Prion diseases

1.INTRODUCTION

A prion is a protein which is morbific, which is the chief construct concerned with this type of disease ( Harris and True, 2006 ) . Humans and animate beings can both go affected by this type of disease ( Tayebi and Hawke, 2006 ) .

Prion Diseases are fatal neurodegenerative diseases, intending that they can do neural loss and harm to the cardinal nervous system and consequence in decease ( Hur et al, 2002 ) . This signifier of disease is infrequent nevertheless they can be acquired and transfered from species to species ( Hu et al, 2007 ) . This category of diseases is linked to the wrong folding of proteins ( Cohen, 1999 ) . Other similar neurodegenrative diseases are Alzhemimers and Parkinsons disease ( Hur et al, 2002 ) . The cause of a prion disease is the prion protein which is found in everyone nevertheless the prion protein in people with a prion disease is mutated, this mutated protein can do a disease as it becomes infective without a nucleic acid ( Westergard et al, 2007 ) .

Neurodegenerative diseases commence from the physique up and the wrong conformational folding of a protein, the biological activity of a protein depends on its correct folding ( Soto et al, 2002 ) . Strong grounds has been found to demo that protein misfolding plays a major function in the pathogenesis of these diseases ( Soto et al, 2002 ) .

Hur et Al ( 2002 ) said that the ground that there has become an increased involvement in Prion diseases in scientific discipline and wellness is because they have characteristic pathophysiology. There are many spreads in the cognition of prion diseases, for illustration the pathogenesis, what causes the mutagenic prion protein and where prion diseases foremost arose from, this has created involvement for many scientists.

The coevals of the prion disease involves a mechanism that changes PrPc to PrPsc in an autocatalytic manner ( Harris and True, 2006 ) . PrPc is said to be the prion protein that has non been affected by any mutants whereas PrPsc the scrapie signifier which is mutagenic. The unnatural signifier of the prion protein is refered to a scrapie as this is where the prion disease was foremost identified in sheep centuries ago ( Hur et al, 2002 ) . Prion diseases can happen in worlds and in animate beings ( Hur et al, 2002 ) .

Prion diseases or catching spongiform brain disorder ( TSE ) can be inherited and can besides be transmited, a common characteristic of the prion disease involves the alteration of the prion protein PrPc to the isoform PrPsc ( Hu et al, 2007 ) as shown in figure one below.

The PrPsc isoform which is known to be the most common characteristic of the prion disease is dominated by a beta sheet incorporating strong H bonds and this construction is twisted ( Harris and True, 2006 ) . Many research workers have found that the strong H bonds make this isoform resistant to digestion protein kinase thousand significance that this protein can construct up peculiarly in the encephalon tissue doing harm to neurones and therefore perchance taking to a prion disease ( Harris and true, 2006 ) . The PrPsc isoform is protein kinase K immune and is non broken down, therefore it progressively builds up in the encephalon tissue of patients with prion diseases and causes farther neurodegeneration ( Hu et al ( 2007 ) .

2. THE PRION PROTEIN ( PRNP )

The prion protein is found on chromosme 20 in mammals, incorporating two coding DNAs ( Nicolas et al, 2009 ) . The 2nd coding DNA is transcribed to bring forth the concluding prion protein ( Nicolas et al, 2009 ) . The prion protein is an extracellular protein ( Nicolas et al, 2009 ) , therefore is located outside and between cells.

There are two points where gylcosalation takes topographic point both contain a-helix countries ( Nicolas et al, 2009 ) . There is an extended N-terminus nowadays, three a-helixes and two -sheets ( Nicolas et al, 2009 ) .

The cardinal portion of the prion protein contains positively charged residues and a hydrophobic part ( of import for protein folding and protein interactions ) ( Nicolas et al, 2009 ) . The concluding portion of the prion protein is made up of an a-helix and two -sheets as shown in Figure one below ( Nicolas et al, 2009 ) .

Nicolas et Al ( 2009 ) said that the agreement of the bases in the prion protein had been maintained through development.

Figure 1: ( a ) The prion protein -sheets shown in bluish, a- helicle parts shown in purple, ( B ) The mutated prion protein found in people with prion diseases, an addition in the beta construction shown in blue.

Hu et Al ( 2007 ) .

3. PROTEIN FOLDING/MISFOLDING

When a protein is produced the concatenation will get down to turn up in to its cardinal agreement a 3D- construction is formed with H bonds doing the protein stable ( Surguchev and Surguchov, 2009 ) .

Proteins endure arrangement alterations before they reach their concluding extremely stable signifier ( Surguchev and Surguchov, 2009 ) .

Amino acid sequences are really of import. Interactions between the correct amino acerb sequences mean that the protein formed will be are more stable than when the amino acid has a mutant ( Surguchev and Surguchov, 2009 ) . The structural agreement of aminic acids and therefore the protein is really of import to the right map of the cellular protein ( Surguchev and Surguchov, 2009 ) .

The amino acerb sequence of the prion protein in humas is shown in figure two below, this amino acis sequence accour in the prion protein in all worlds a chabge in this sequence could ensue in a prion disease.

4. PROTEIN FOLDING/MISFOLDING

When a protein is produced the concatenation will get down to turn up in to its cardinal agreement a 3D- construction is formed with H bonds doing the protein stable ( Surguchev and Surguchov, 2009 ) .

Proteins endure arrangement alterations before they reach their concluding extremely stable signifier ( Surguchev and Surguchov, 2009 ) .

Amino acid sequences are really of import. Interactions between the correct amino acerb sequences mean that the protein formed will be are more stable than when the amino acid has a mutant ( Surguchev and Surguchov, 2009 ) .

The structural agreement of aminic acids and therefore the protein is really of import to the right map of the cellular protein ( Surguchev and Surguchov, 2009 ) .

5. Mutant

The wrong folding of a protein can happen as a consequence of mutants in the protein itself of in due to errors in protein synthesis ( Surguchev and Surguchov, 2009 ) .

If these mistakes are made and do the amino acid sequence to alter so wrong turn uping can happen taking to an unstable construction and the protein can construct up going harmfull ( Surguchev and Surguchov, 2009 ) .

The amino acerb construction of the prion protein found in all worlds is shown in figure two antecedently.

6. History

The first description of scrapie the prion disease found foremost found in sheep was in 1752 and writers had described the disease to be known for around 40 old ages ( Schneider, 2008 ) . Scrapie has hence been known for over 200 old ages throughout the universe ( Tayebi, 2006 ) . In 1969 BSE occurred in many cowss in the uk turning in to an epidemic ( Tayebi, 2006 ) . Literature at this clip on prion diseases was chiefly done by economic experts for illustration husbandmans or Shepards, scientists were unknown of the disease at this clip because husbandmans wanted to maintain it a secret as their quality of life was reliable on income from purchasers ( Schneider, 2008 ) . Therefore all malformations were kept quiet to purchasers so no money was lost ( Schneider, 2008 ) .

The absence of awarness of scrapie at this clip besides accounted for the fact that research in the likely causes and the genetic sciences of scrapie did non get down until much later on ( Schneider, 2008 ) .

In the nineteenth century many scientists proposed that scrapie was so infective and proposed that its transmittal was linked to sexual intercourse ( Schneider, 2008 ) . However many other research workers were definite that the disease occurred spontaneously ( Schneider, 2008 ) . In the early nineteenth century it was besides thought that the disease was familial and in 1998 nutrient was thought to persue an acquired signifier of the disease ( Schneider, 2008 ) .

7. Development

To analyze the development of the prion protein in different species a phylogenic tree was done which links the prion strains together based on similarities which could alter throughout development. To make this the pubmed web site has been used to happen different prion protein sequences which were similar to the human prion protein. All of these MRNA were so put in to a programme called clustal

( hypertext transfer protocol: //www.ebi.ac.uk/Tools/clustalw2/index.html ) which matches sequences of MRNA harmonizing to similarities

Figure 3: Phylogenic tree demoing evolutionary relationships between the prion protein.

Figure three above shows a phylogenic tree which shows relationships/ similarities within the prion protein in different species which has been carried throughout development.

The human prion protein seems to be linked to the gorilla prion protein significance that there are similarities here which makes sense harmonizing to other evolutionary similarities with adult male and gorillas. Although non many surveies have shown that prion disease affect the gorilla it would look from the phylogenic tree that as the prion is similar to the homo that the gorilla may hence be susceptible to mutants that cause prion diseases in worlds. Research could be doen into the prion protein in the gorliia compared to adult male.

As described subsequently on it has been shown that the coney shows opposition to prion diseases ( Vorberg et al, 2003 ) . Figure three above links the coney to the cat and fox indicating that possibly the similarities in this prion/ a common sequence throughout development could intend that the prion protein in these species besides have prion disease opposition. The construction of the prion protein in the cat and fox could be similar to the coney exposing opposition. Research could be done on the act prion and the fox prion to see if there are really similarities with these prion proteins farther work into this could assist with the therapies of prion diseases. Although figure three above does demo some penetration into the development of prion disease mistakes could hold been made in the sequences of the MRNA found via the pubmed web site. These sequencing mistakes may therefore green goods inaccuracies within the phylogenic tree above for illustration some species may non infact hold prions similar to other species but sequencing mistakes have shown that they do.

The prion protein from many different animate beings has been studied by cloning/sequencing ( Loftus and Rodgers, 1997 ) . Similarities in the construction and alliance of the prion protein sequencves have been found between many prion proteins cloned from mammals ( Loftus and Rodgers, 1997 ) . This can besides be shown in figure three above.

A method into analyzing the differences between the prion protein and the mutated prion protein can be done by comparing prion protein cistrons from different mammals to happen of import parts that have remained throughout development and therfore could be of import in the opposition to the mutated prion protein ( Loftus and Rodgers, 1997 )

A negative to this attack is that the big sum of similarities between prion cistrons in different species has made it hard to observe of import parts of the pi-meson protein that have been reserved through development ( Loftus and Rodgers, 1997 ) .

The coney prion protein cistron is really of import when analyzing comparings between prion cistrons because it is said to be immune from prion disease infection therefore may hold a different construction compared to prion cistrons from other species ( Loftus and Rodgers, 1997 ) . A increased intelligence in the construction and map of the prion protein could therefore aid in the hereafter of prion diseases in worlds ( Loftus and Rodgers, 1997 ) .

A old survey of development doing comparings between all prion cistrons implied that the coney prion cistron was distinctially different that other members in its group which contained other mammals such as sheep and hogs ( Loftus and Rodgers, 1997 ) .

The chief differences are shown further on in subdivision 13 figure eight where Loftus and Rodgers ( 1996 ) have described codon 107 and 173 as being the chief diffrerence in comparing to the human prion protein amin acerb sequence shown in figure two antecedently which could contrinute to the coneies opposition.

8. PATHOPHYSIOLOGY

Many hypotheses have been developed in order to seek and explicate prion diseases, nevertheless none have been to the full accepted. The most common hypothesis is the Prion hypothesis ( Basakov and Breydo, 2007 ) . This suggests that the agent doing neurodegeneration is the prion protein but the signifier that is affected by a/several mutants or missing a nucleic acid ( Westergard et al, 2007 ) . This escapes protein kinase K digestion and remains in encephalon tissue doing neural harm ( Yull et al, 2008 ) . This hypothesis besides suggests that the agent doing the disease is PrPsc which duplicates ( Baskakov and Breydo,2006 ) .

A figure of hypotheses have hence been made in order to seek and explicate the pathogenesis of prion diseases ; they all correlate to the prion protein hypothesis bespeaking that the mutated prion protein PrPsc is involved in the pathogenesis. Figure four below shows a flow diagramme of some of the tracts.

Nicolas ( 2009 ) reported a survey in the 1990s to happen out the proposed maps of the prion protein. A break of the prion protein in mice showed alterations in the behavior and cognitive disfunctions they besides showed an addition in susceptibleness to oxidative emphasis ( Nicolas, 2009 ) . This together with other surveies has lead to the possible accounts for the functional function of the prion protein and hence the pathohysiology of prion diseases.

8.1 Oxidative emphasis

One hypothesis links the pathogenesis to oxidative emphasis and suggests that PrPc is involved in doing certain that cells do non go damaged by oxidative emphasis ( Westergard et al, 2007 ) . The alteration in the map of PrPc for illustration by a mutation/ misfolding may hence be linked to the public presentation in disease ( Westergard et al, 2007 ) . Oxidants are produced as the consequence of another action in respiration normally by unnatural respiratory forms in many people with neurodegenerative diseases ( Hur et al, 2002 ) . The sum MDA nowadays can bespeak oxidative emphasis ( Hur et al, 2002 ) . MDA ( Malondialdehyde ) is a reactive aldehyde which causes toxic emphasis in cells and as a consequence generates free groups, degrees of MDA have been found a higher degrees in scrapie septic mice demoing an engagement of oxidative emphasis ( Hur et al, 2002 ) .. It has hence been suggested that the normal prion protein PrPc protects cells from oxidative emphasis and hence an unnatural signifier of this protein will let oxidative emphasis and hence cause harm to neurones perchance taking to a prion disease ( Westergard et al, 2007 ) .

Evidence has besides been found that the PrPc protein has SOD ( Superoxide dimutase ) activity and that PrPc uses detoxification to acquire rid of any O species that could respond and do oxidative harm in cells ( Westergard et al, 2007 ) . However other surveies have found grounds against this therefore farther work demands to be done to corroborate this. One manner that the PrPc protein has been found to halt oxidative harm is by increasing the cell constituents such as proteins, for illustration a combination of copper-zinc SOD that can take and damage any go arounding reactive oxidative species ( Westergard et al, 2007 ) . Therefore a mutated from of the prion protein would neglect to make this significance that oxidative species remain in encephalon tissue doing neural harm ( Westergard et al, 2007 ) . However Westergard et Al ( 2007 ) said that these consequences had failed to be a regular determination in other scientific research.

8.2 Heavy ions

8.2.1 Copper

Copper may besides be involved in the pathogenesis of prion diseases. Copper is a substance necessary to the map of many enzymes ( Westergard et al, 2007 ) . Abnormal metamorphosiss in the organic structure have been linked with many neurodegenerative diseases ; it is thought that Cu ions can alter the belongingss of the normal prion protein ( Westergard, 2007 ) .

Many scientisits have found that the OR portion of the prion protein can adhere to copper ions and as a consequences can therefore alter the degrees inside the cell ( Nicolas, 2009 ) . In some surveies the measure of Cu inside the encephalons of mice with a mutated prion protein have shown much lower degrees compared to healthy mice proposing a function of reduced degrees of Cu in the pathophysiology of prion diseases ( Nicolas, 2009 ) . However these consequences have failed to replicated in other surveies, bespeaking that the function of Cu should be farther investigated.

8.2.2 Iron

Hur et Al ( 2002 ) have reported that Fe is involved in neurodegenerative diseases, scientists have shown that the sum of Fe is much higher in the encephalons of people affected with the disease. Iron is needed for free extremist formation, reasoning that there is a nexus to oxidative emphasis and neural harm hence lending to prion diseases ( Hur et al, 2002 ) . Iron is besides said to do an addition in the O toxicity through a reaction catalyzed by ion, O and H peroxide accompanied by Fe can turn in to really unsafe species doing oxidative emphasis and neural harm ( Hur et al, 2002 ) .

8.2 Mitochondrions

A figure of surveies have shown that unnatural belongingss of the chondriosomes were found in the encephalons of patient affected by a prion disease. A nexus to this has hence been correlated to the function of this in the development of prion diseases. Hur et Al ( 2002 ) found an addition in the lipid peroxidation in the encephalons of affected patients, they besides found unnatural constructions of chondriosomes particularly in the hippocampus and intellectual nerve cells of scrapie infected patients.

8.3 Inflammatory processors

A function of the immune system in the extension of prion diseases has been studied and suggests that inflammatory constituents for illustration cytokines play a portion in doing neural harm ( Hur et al, 2002 ) . The function of PrPc and the immune system still remains unknown nevertheless some grounds has been found to back up this ( Hur et al, 2002 ) . Evidence has been found that shows that interleukin 1 a and tumour mortification factor were significantely higher in patients with the disease compared to controls ( Hur et al, 2002 ) . There has besides been found to be an addition in COX-2 in affected people, this may be associate to the pathogenesis of prion diseases by doing the activation of inflammatory processors ( Hur et al, 2002 ) .

8.4 Apoptosis/necrosis

A theoretical account of cell decease has been suggested for the pathogenesis of prion diseases. This sufggestes that cell decease tracts for illustration programmed cell death ( programmed cell decease ) and mortification ( early cell decease ) play a portion in prion diseases. A higher degree of Ca is linked to mortification and this has been found to be the instance in scrapie infected people ( Hur et al,2002 ) .

8.5 The synapse

In all mammals the prion protein exists in a assortment of tissues for illustration the bosom and neurones ( Nicolas et al, 2009 ) .

In neurones the prion protein is found dominantly in the synapse for illustration in axons and besides in dendritic countries ( Nicolas et al, 2009 ) . The normal functional function of the prion protein at the synapse is still unknown and has caused many arguments ( Nicolas et al, 2009 ) . However in worlds with CJD the mutated prion protein accumulates in the synapse, proposing that this physique up has a function in neural loss and devolution ( Nicolas et al, 2009 ) .

The engagement of the prion protein in synaptic transmittal is ill-defined, but many suggestions have been put frontward ( Nicolas et al, 2009 ) .

The prion protein could help with the release of neurotransmitters from the synapse, which is supported by grounds which has shown that synapsin Ib ( a protein that regulates release of neurotransmitter from the synapse ) can interact with the prion protein, hence a mutated prion protein would interfere with synapsin Ib and hence neurotransmitter release ( Nicolas et al, 2009 ) .

Nicolas et Al ( 2009 ) said that when PrPc is non present the look of receptors involved in neurotransmission can be changed.

The prion protein besides has contact with proteins that are involved in the formation of the synapse, hence proposing a functional function of the prion protein in the edifice and support of the synapse ( Nicolas et al, 2009 ) . Therefore a mutated prion protein significance that neural transmittal would be affected accounting for motor disfunction in patients with prion diseases.

8.6 The cell rhythm

The prion protein has been found to be of import for the cell division portion of the cell rhythm in many cells ( Nicolas et al, 2009 ) . The manner the prion protein behaves in spliting cells can change depending of the look of it ( Nicolas et al, 2009 ) . The prion protein has a certain function in spliting cells and it combines with other elements to modulate division and distinction ( Nicolas et al, 2009 ) . Therefore a mutated signifier of the prion protein could so cut down or get rid of cell division.

8.7 Ligands of the prion protein

Many surveies have found many ligands associated with the prion protein ( Nicolas et al, 2009 ) . The effects of the interactions of the prion protein with these ligands is still unsure and consequences found from the interactions have non been replicated in similar surveies ( Nicolas et al, 2009 ) .

An interation of the prion protein with the lamin receptor has been found to be linked to neurodegeneration by driving the change of the prion protein to a mutated signifier ( Nicolas et al, 2009 ) .

9. ANIMAL AND HUMAN PRION DISEASES

There are many different types of prion diseases that have been found in worlds and animate beings. One illustration in Humans is Creutzfeldt-Jakob disease which is really frequent and another illustration is Kuru ( Hu et al, 2007 ) . Examples of prion diseases concerned with animate beings include scrapie which was the first instance found in sheep many old ages ago ( Hur et al, 2002 ) . Bovine spongiform brain disorder is besides an carnal prion disease ( Hu et al, 2007 ) . Different signifiers of prion diseases both human and carnal signifiers are associated with different signifiers of PrPsc ( Soto et al, 2002 ) .

9.1 Animal

9.1.1 Scrapie

Scrapie was the first type of prion disease found in sheep and caprine animals many centuries ago ( Hur et al, 2002 ) . Johnson ( 2005 ) said that it was given the name scrapie because of the alteration in features that the diseases caused. For illustration the changeless scraping of the sheeps fleecy coat, the sheep besides showed a inbalanced walk ( Johnson, 2005 ) . How the diseases foremost got transmitted in to sheep is unknown nevertheless sheep exposed to set down for their graze showed an infection in the oral cavity and tonsils, the disease was besides found to be transmitted to immature sheep by parents/other sheep with the disease ( Johnson, 2005 ) .

9.1.2 Bovine Spongiform Encephalopathy ( BSE )

This signifier of carnal prion disease is good known as Mad cow disease ( Hur et al, 2002 ) . The first instance of this was found inn 1985 and in the 1990s there was an eruption of this ( Johnson, 2005 ) . In 1986 in the United Kingdom there was a epidemic where many cattles were affected by BSE ( Tayebi, 2006 ) . It was thought that the disease may hold been passed on to cattles by the ingestion of contaminated bones/meat from dead sheep Federal to overawe a 2nd hypothesis implies that a individual instance of this appeared in a one cow which started the eruption ( Johnson, 2005 ) .

9.2 Human

9.2.1 Creutzfeldt-Jakob Disease ( CJD )

This is the most frequent signifier of prion diseases and incidences of this have been found all over the universe ( Hu et al, 2007 ) .

Many mutants in the PrPsc protein in prion disease have been found and linked to the different signifiers of Prion disease. The polymorphism at codon place 129 in the prion protein has been found to be involved in the different looks of Creutzfeldt-Jakob Disease ( Mikol, 1999 ) doing different characterisitics in the disease. CJD is the most frequent type of prion diseaes ( Korth and Peters, 2007 ) . This mutant is shown in figure two below.

9.2.2 Familial CJD ( FCJD )

This signifier of prion disease occurs at an earlier phase in life and is hence drawn-out ( Mikol, 1999 ) . The sum of mutated prion protein has been found to be lower than in ither signifiers of CJD

Mutants and interpolations have been found to be involved in another from of human prion disease known as familial Creutzfeldt-Jakob Disease ( Miko, cubic decimeter 1999 ) . A common mutant at codon 178 had been found in the first instance, this mutant is besides shown on figure two. An interpolation found in many instances is the interpolation of 144 bases this clip in codon 53 non 129 ( Mikol, 1999 ) .

9.2.3 Fatal Familial insomnia

This signifier is highly uncommon and has been found throughout history in less than twelve households ( Mikol, 1999 ) .

Relation to this disease and a mutant at codon 178 has been found and besides a homozygous methionine at 129 has been found linked to this disease ( Mikol, 1999 ) .

These mutants are shown in figure seven below.

9.2.4 Gerstmann-Strussler-Scheinker Disease ( GSS )

This type of prion disease can be linked to the physique up of amyloids in encephalon countries ( Mikol, 1999 ) . A common mutant is at codon 102, shown in figure seven below ( Mikol, 1999 ) .

9.2.5 Sproadic CJD ( SCJD )

This signifier of the disease is universe broad and occurs in both sexes ( Johnson, 2005 ) . This signifier of this disease accounts for an estimated 85 % of prion diseases ( Wadsworth and collinge, 2007 ) . It is termed sporadic because of its unexpected visual aspect from knowwhere in worlds. A hypothesis suggests that a prion protein mutant in this signifier of the disease is bodily or that the alteration in the the mutated signifier is rare and conjectural ( Wadsworth and Collinge, 2007 ) . It normally occurs in older ages around 60 old ages, characteristicall characteristics such as musculus spasm and disturbed kiping forms, in some instances there is loss of seeing ( Johnson, 2005 ) .

9.2.6 Variant CJD ( VCJD ) .

This signifier of the disease was foremost found in 1994 and has different features to SCJD ( Johnson, 2005 ) . It is found in younger work forces and adult females ( Johnson 2005 ) . A hypothesis for the transmittal is thought to be via people eating meet infected by the disease ( Johnson, 2005 ) . Over one hundred and 50 incidents of VCJD have been reported in the United Kingdom ( Korth and Peters, 2007 ) . The distribution of incidences in the UK is shown in figure five below.

Baket and Ridley ( 1996 ) ,

Experiments have proved that this signifier of prion disease is caused by the same prion protein mutant that formed the epidemic in cowss in the united land ensuing in BSE described in 9.1.2 ( Wadsworth and collinge, 2007 ) .

The long incubation clip that prion disease have has been a major concern for many old ages to the wellness of worlds as it is believed that many persons will finally be contaminated with a prion disease from cowss through the major epidemic ( Wadsworth and collinge, 2007 ) . Many persons in the United Kingdom could hence be keeping the disease and infact go throughing it on via blood contributions and organ contributions which could impact the United Kingdoms poulation and besides others throughout the universe in the hereafter ( Wadsworth and collinge, 2007 ) .

There is an mean age that the disease affects at 26 old ages most patients are at the deadly phase at 68 old ages ( Wadsworth and collinge, 2007 ) .

9.2.6 Kuru make better! ! !

Kuru is an acquired from of the prion disease under the category of worlds, this can be characterised by kuru plaques which have been found in 70 per centum of people with this signifier of the disease ( Mikol, 1999 ) . There has become recent involvement kuru because of a suggested increased opposition to this and an eruption of this disease in England ( Goldfarb, 2002 ) . There is besides a suggested nexus between this signifier of the disease and Vcjd ( Goldfarb, 2002 ) . This disease has the feature of rapidly damaging the cardinal nervous system and it can do decease ( Goldfarb, 2002 ) . There was an eruption of kuru which killed many people in New Guinea most of these people were from a little country populated by a civilization known as the Fore people ( Goldfarb, 2002 ) . Fore is a rock age civilization that before cannibalism was stopped in the 1950s Ate dead relations ( Goldfarb, 2002 ) .

Kuru is thought to hold been transmitted to worlds through cannibalism, but it is non widely known how prion diseases foremost developed in worlds and animate beings ( Goldfarb, 2002 ) . It was pursued in this civilization to eat relations who had died, hence ensuing in the disease go throughing from individual to individual ( Mead et al, 2009 ) . By the late 1950s there was a halt to cannibalism and correlating with this the figure of people deceasing with kuru decreased besides no individual after the `1950s had developed Kuru ( Goldfarb,2002 ) . However how kuru foremost affected the Fore people is still ill-defined ( Goldfarb, 2002 ) . A decision has been made that the eruption of this disease must hold started with one individual who had died from sCJD and so was eaten by cannibalism, hence go throughing the disease on ( Goldfarb, 2002 ) . The decrease in people affected with this disease has led people to believe that there is someway a opposition that has been gained throughout development ( Mead et al, 2009 ) . The suggested opposition to kuru can nevertheless be questioned, for illustration is there infact a developed opposition to kuru or is infact the decreased incidences of kuru due to the halt of cannibalism.

Many surveies have aimed to happen the mutants involved in kuru.

A methionine/valine ( M/V ) in the 129 codon of the prion protein has been recorded in many people affected by kuru ( Goldfarb, 2002 ) . Goldfarb ( 2002 ) found that in the Fore civilization the methionine/methionine ( M/M ) was popular in patients enduring from kuru at an early age and that a alteration to methionine/valine showed that kuru developed at a ulterior age. M/M has been found to do it more likely that that person will be affected by kuru and besides be affected earlier on in life ( Goldfarb, 2002 ) . A heterozygous prion has been found to protect the person from deriving kuru ( Mead et al, 2009 ) .

Mead et Al ( 2009 ) besides studied another polymorphism which was thought to be linked to kuru, the G127V polymorphism. They concluded that this G127V cistron is an agent gained that provides opposition to kuru in a heterogenous signifier and is non a mutant that can be passed on which could hold caused the kuru eruption ( Mead et al, 2009 ) .

11. Clinical Feature

There are three chief pathological features found in the encephalon of patients with prion diseases ( Mikol, 1999 ) . A squashy expression is a really common characteristic where the encephalons of patients enduring from a prion disease through a microscope expression like a sponge for illustration with holes in, besides referred to as spongosis ( Mikol, 1999 ) . The most common characteristic is the loss of neurones which is particularly noticed in the neopallium, cerebellum and besides in the thalamus ( Mikol, 1999 ) . Gliosis is abundant, this is where astrocytes in the encephalon suffer from proliferation ( Mikol, 1999 ) .

The most common clinical characteristic of prion diseases is the perturbation of motor map, for illustration nonvoluntary motions which can be arrhythmic, behavioral and personality alterations have besides been found in many surveies. Maltte et Al ( 2006 ) said that CJD can be has the clinical features of dementedness, twitchy motions ( mycolonus ) . Ocular distruptions have besides been found ( Maltte et al, 1999 ) .

Maltte et Al ( 2006 ) classified CJD as a motion upset.

Mycolonus is really common as a clinical characteristic of prion diseases and is linked to many instances of all three types of CJD ( Maltte et al, 2006 ) . Maltte et Al ( 2006 ) found that this was more common in patients showing methionine/methionine at place 129, which every bit explained antecedently is linked with an increased succeptability to the development of a prion disease. Maltte et Al ( 2006 ) as described dystonia as a clinical feature for illustration patients can develop a dispositional position at an early phase. Tremors can besides happen as an early characteristic in some instances of sporadic CJD ( Maltte et al, 1999 ) .

Disturbed motions described above can be accounted for by neural loss in the cerebellum ( Mikol, 19999 ) . The cerebellum is the country of the encephalon that controls motion hence any harm to nerve cells would take to motions which are non coordinated and inaccurate, besides known as ataxy ( Bear et al,2001 ) . The cerebellum contains the highest figure of nerve cells, accounting for 50 % of nerve cells in the CNS ( Bear et al, 1999 ) . The alteration in behavior besides seen in many patients with prion diseases can be explained by the loss/damage to neurones in the prefrontal cerebral mantle of the encephalon which controls many cognitive maps for illustration commanding personality ( Bear et al, 1999 ) . The sidelong cerebellum is involved in organizing joint motions hence harm to this country would explicate why some patients with prion disease are unable to walk ( Bear et al, 1999 ) .

Many scientists have done research in order to happen out the clinical features of patients with prion diseases and the grounds for the clinical alterations. The clinical features found can be linked to the pathological characteristics in the encephalons of people with prion diseases.

May et Al ( 1968 ) studied a household affected by a prion disease, clinical features such as sudden unmanageable motions and look in the face such as the ability to smile were lost. Pathological characteristics such as the loss of nervousnesss were found ( May et al, 1968 ) . These characteristics can be linked to neural loss in specific parts of the encephalon, for illustration break of walking can be linked to the loss of nerve cells fro illustration in the cerebellum of the encephalon which controls motion ( Bear et al, 1999 ) .

A survey by collinge et Al ( 1996 ) found that all acquired instances of prion diseases showed the clinical feature of ataxy and psychological break was a common feature. Collinge et Al ( 1996 ) came to a decision that it is the mutated prion protein that infact may be the constituent that produces the clinical characteristics/ phenotypes shown in people with a prion disease.

Collinge et Al ( 1996 ) studied the different strains of the prion protein in worlds as merely two have been found so far which are linked to the different CJD types.

Variant CJD was so tested by Collinge et Al ( 1996 ) to see whether separate strains are found.

It was found that CJD is associated with three different markers via a western smudge analysis ( Collinge et al, 1996 ) . Types one and two are shown in sporadic CJD and type three shown in acquired instances ( collinge et Al, 1996 ) . The two separate sets that have been shown to be linked to SCJD and represent either homogenisity or heterogenisity ( Collinge et al, 1996 ) .

Collinge et Al ( 1996 ) tested the mutated prion protein from a sample from a VCJD patient. It was found that variant CJD shown set features that were different that any other sets, reasoning that VCJD is a a clearly different type of prion disease which is connected to a unknown prion strain ( Collinge et al, 1999 ) .

Collinge et Al ( 1999 ) besides concluded that acquired instances of prion diseases have a clearly different phenotype demoing marks of ataxy and patients can go psychologically disturbed. These clinical characteristics found are besides common characteristics of prion diseases in Humans.

Hsiao et Al ( 1994 ) found that neural loss occurred in mice when inserted with a mutated prion protein losing a nucleic acid. Two lines of transgenic mice with a high sum of the mutated prion protein developed ataxy and had stiff motions ( Hsiao et al, 1994 ) which are once more clinical characteristics of a prion diseases in worlds.

Dossena et Al ( 2008 ) found that transgenic mice with a mutated prion protein were did non hold physiological reactions in their pess and were besides unbalanced ; they had an unnormal position which twisted to one side. The mice were besides unable to mount up a grill vertically, this indivcates motor disfunction which is a clinical characteristic shown in worlds with CJD ( Dossena et al, 2008 ) .

Dossena et Al ( 2008 ) found that transgenic mice who were homozygous developed clinical characteristics linked to CJD much earlier than heterozygotes demoing a mucher faster neurodegeneration and making the fatal phase at 130 yearss.

Trangenic mice with a mutant prion protein below endogeneous degrees stayed healthy for a longer period before clinical sighns started to demo ( Dossena et al, 2008 ) . This supports the hypothesis that a larger sum of the mutab=nt prion protein leads to earlier and quicker neurogeneration ( Dossena et al, 2008 ) .

12. ANIMAL MODELS

Many experiments have been carried out on animate beings by scientists which are reflected in worlds.

12.1 Kuru came from ingestion of a individual individual with sprodiac CJD?

Wadsworth et Al ( 2008 ) carried out a Kuru animate being theoretical account to turn out that the prion protein in kuru is clearly different from the prion protein in Variant CJD, but similar to the prion protein in Sporadic CJD.

There has become recent involvement in kuru because of the big sum of people who had been affected by variant CJD in the United Kingdom and the idea that the mutated prion protein is caused by a indistinguishable prion protein doing BSE.

A batch of involvement has been shown in Kuru due to the fact that it had suposebly arose from eating a individual with the sprodiac signifier of CJD, this supports the hypothesis discussed before by Goldfarb ( 2002 ) and Mead et Al ( 2009 ) .

Four major mutated prion proteins have been found so far associated with prion diseases all demoing different fragment sizes on immunoblots, types one to three have been found to be linked with sprodiac CJD and type four with variant CJD ( Wadsworth et al, 2008 ) . Types one and four have been found merely specifically in people with a homozygous methionine codon 129, type three has been found to be associated with heterozygous valine/methionine at codon 129 ( Wadsorth et al, 2008 ) . In the survey performed by Wadsworth et Al ( 2008 ) they studied three encephalon samples affected by kuru demoing that the Prp fragments are similar to type two and type three. They said that the information they found was accordant with findings from other surveies demoing that there is close resemblance of the mutated prion protein in kuru and variant CJD. They concluded from this that kuru hence originally came from ingestion of a individual with sprodiac CJD ( Wadsworth, 2008 ) , as besides described in subdivision 9.2.6.

12.2 A mutated prion protein causes devolution and loss of cerebellar Purkinje fibers?

Sakaguchi et Al ( 1996 ) preformed an carnal theoretical account to demo that a mutated prion cistron in older mice ( with a homozygous PrP cistron ) causes the loss of Purkinje fibers which is a clinical feature associated with prion diseases in worlds.

This cistron in the mice studied was replaced by a drug immune cistron ( Sakaguchi et al, 1996 ) .

Correlating to old surveies they found that homozygous loss of the prion protein cistron did non hold any harmfull consequence on the mice and they were immune to any affects from a prion disease, hence associating to the hypothesis that it is the prion protein that causes the prion disease ( Sakaguchi et al, 1996 ) .

Homozygous, heterozygous and healthy mice were studied for a long continuance of clip. For a twelvemonth the homozygous mice grew in an expected mode nevertheless at 70 hebdomads old they showed some marks of clinical characteristics of prion diseases for illustration disrupted motion and walking, at 90 hebdomads the mice fell over on a regular basis ( Sakaguchi et al, 1996 ) . These consequences were peculiarly apparent in the homozygous mice ( Sakaguchi et al, 1996 ) . None of the hellthy or heterozygous mice showed any of these symotoms until at least over 90 hebdomads old ( Sakaguchi et al, 1996 ) . This supports work explained previosly by Goldfarb ( 2002 ) that there is an increased succeptibility to a prion diseases with a homozygous codon 129, heterogenisity shows that the symptoms of prion disease occur at a ulterior age.

The encephalons of these mice were tested for clinical characteristics, an apparent characteristic found was devolution in the cerebellum of the barin ( Sakaguchi et al, 1996 ) . These characteristics are besides common to the characteristics shown in worlds with a prion disease. The encephalons besides showed noticeable loss of purkinje fibers.

The Purkinje cells contain tonss of the prion protein, therefore these consequences show that a mutated prion protein, peculiarly a homozygous signifier causes devolution and therefore a prion disease ( Sakaguchi et al, 1996 ) .

However this carnal theoretical account can be critisised as infact two other surveies with mice did non bring forth any of these clinical characteristics even after ninty hebdomads, they supported this and said that many conditions such as the genteelness conditions for illustration could hold accounted for this and that infact the mice could therefore developo the clinicakl features at an even older age ( Sakaguchi et al, 1996 ) . They besides said that this difference found may be due to little differences in the construction of the mutated cistrons ( Sakaguchi et al, 1996 ) .

13. RESISTANCE TO PRION DISEASES

No animate beings have been found to be immune to prion diseases apart from coneies ( Vorberg et al, 2003 ) . Rabbits have been found by many scientists to hold a certain species barrier to TSE ( Vorberg et al, 2003 ) .

They have been found to surive through initiation of the mutated prion proteins that from prion diseases such as kuru and CJD ( Vorberg et al, 2003 ) . Vorberg et Al ( 2003 ) provided grounds that implied that the opposition of coneies to the infection of a prion disease agent is due to prion protein amino acids specific to the coney and non to the TSE used to bring on the disease. The specific amino acids mean that the ensuing PrP construction is unable to turn up in to to a mutated prion protein able to organize the disease ( Vorberg et al, 2003 ) . Vorberg et Al ( 2003 ) have shown that the coney prion protein does non organize an unnatural prion protein in neuroblastoma cells infected with mouse scrapie, the coney besides shows no clinical features. However these consequences have merely been found by probe the opposition of coneies from the initiation of a catching prion protein which is thought to be the chief agent responsible for prion diseasse susceptibleness. It is non know whether the coney will organize SCJD and this could go on at any point in the hereafter. This survey has merely used one cell line it has non been shown that the prion disease will non organize in any other cell line in the coney.

Zhang ( 2010 ) studied the NMR constructions of the prion protein in the coney and found that the construction of the coney prion protein was highly stable, a salt span found specifically in the coney prion protein between plays a function in this stableness doing it withstand mutants.

They examined the prion protein at the molecular degree. They found that mutant in people with prion diseases make some H bonds/salt Bridgess broken which normally account for the stableness of the prion protein ( Zhang, 2010 ) . Therefore the mutated prion protein is much less stable than the normal prion protein ( Zhang, 2010 ) .

As the prion cistron in the coney is thought to be immune from prion infection it can be really utile in comparing with prion cistrons from other species in order to see the differences for illustration the differences in the construction ( Loftus and Rodgers, 1996 ) .

Loftus and Rodgers ( 1996 ) studied the coney prion cistron. They found that the coney prion cistron was similar in the construction and in their alliance to prion cistrons isolated from other species ( Loftus and Rodgers, 1996 ) . They found a splicing site in the cistron that has besides antecedently been found in the human prion cistron and besides in the rat, they besides found the at the cistron gas all the characteristics of prion cistrons in other species for illustration N-terminals ( Loftus and Rodgers, 1996 ) .

The opposition to infection via transmittal from a host prion to bring on a prion disease is determined on whether or non the prion protein can be converted to the mutagenic signifier, this is dependent on the amino acerb sequence of the prion protein that may go septic and besides the prion protein that is used to infect ( Loftus and Rodgers, 1996 ) .

Loftus and Rodgers ( 1996 ) therefore said that the opposition of the coney by prion infection must be caused by differences in the amino acerb sequence of the prion cistron in coneies that enables it to defy prion infection.

The prion amino acerb sequence from the coney was hence studied against the amino acerb sequences of the prion from the human and monkey as these species were unable to bring on prion infection in to coneies ( Loftus and Rodgers, 1996 ) .

Figure 7: Amino acerb sequence of the coney prion protein Foregrounding the chief differences to the human prion protein shown in figure two antecedently. The chief differences as described below are highlighted in ruddy codon 107 and bluish 173.

Loftus and Rodgers ( 1996 ) found that an obvious difference in the amino acerb sequence of the coney prion protein was at codon 107 and 173. Codon 107 was particulary of involvement as it is thought to be involved in the stableness of the prion protein ( Loftus and Rodgers, 1996 ) . A aminic acid permutation 107 was given to monkeys as was found to confabulate hapless transmittal of prion from worlds into monkeys.

14. A CONFORMATIONAL Disease

Prion diseases and many other diseases for illustration Parkinsons disease can besides be know as a conformational disease due to the fact that there is a build up of the protein that is falsely folded ( Surguchev and Surguchov, 2009 ) .

In add-on to the physique up of these proteins in the encephalon which causes a prion disease the physique up of these proteins can besides happen in many other parts of humans/animlas including the oculus and many parts of the oculus ( Surguchev and Surguchov, 2009 ) .

The oculus can hence be really of import in the probe of prion diseases ( Surguchev and Surguchov, 2009 ) .

Figure 4 below shows how the wrong folding of a protein can take to an change in to pathological signifier. A conformational alteration is the chief manner that neurodegenerative diseases arise.

Protein that are vunerable to construct up can organize starchlike filaments as shown below ( Surguchev and Surguchov, 2009 ) . These are associated with neurodegenerative diseases.

The amino acerb sequence of the protein determines what pathway leads to the physique up, this can hence be changed by a mutant ( Surguchev and Surguchov, 2009 ) . This can be shown in prion diseases where a mutant at place 129 can do CJD ( Mikol, 1999 ) . These mutants which cause wrong folding can do decease of a cell by bring oning emphasis on the quality control portion of the cells development ( Surguchev and Surguchov, 2009 ) .

14.1 The oculus

The oculus can be used to analyze protein construct up associated with neurodegenerative diseases ( Surguchev and Surguchov, 2009 ) . Disturbing protein interactions that normally occur in the lens can ensue in the buils up of proteins and the constitution of cataract, which can be watched easy in alive animate beings ( Surguchev and Surguchov, 2009 ) . Many advantages of the oculus make it suited for analyzing the physique up of proteins associated with the developmet of neurodegenerative diseases ( Surguchev and Surguchov, 2009 ) .

The retina is known as the easiest portion of the encephalon which can be used to analyze conformational diseases such as in prion diseases and can assist with drug development ( Surguchev and Surguchov, 2009 ) .

14.1.1 The retina

The prion disease Scrapie can do many oculus deformaties particularly in the retina ( Surguchev and Surguchov, 2009 ) .

Surguchev and Surguchov ( 2009 ) found that when hamsters were induced with the scrapie mutant there was a clear loss of rod cells and after 10 hebdomads the atomic bed on the exterior of the oculus was the lone portion Lashkar-e-Taiba.

In sheep which are affected by this disease the mutated prion protein was found to construct up in parts of the oculus including in the ocular fiber ( Surguchev and Surguchov, 2009 ) .

However although the mutated prion protein has been found to construct up in the retina it has non been found to do devolution of the retina ( Surguchev and Surguchov, 2009 ) .

Further research could be done as to why the PrPsc causes neural devolution, nevertheless when PrPsc builds up in the retina it does non do devolution of the retina.

The physique up of PrPsc in the oculus has besides been shown in worlds. Worlds affected by CJD have been found to endure from a physique up of the mutated prion protein in the ocular nervus every bit good as the retina, which is thought to correlate with the fact that the prion protein has built up in the encephalon and so through the ocular nervus ( Surguchev and Surguchov, 2009 ) .

15. Treatment

Many marks for the therapy of prion diseases are described below.

1. Making the prion protein cistron soundless by RNA which aims to halt prion protein transmutation in to the mutated signifier ( Korth and Peters, 2007 ) . Side effects to this therapy are really little ( Korth and Peters, 2007 ) .

2. Disabling prion protein transmutation into the mutagenic signifier by utilizing antibodies ( Korth and Peters, 2007 ) . A major disadvantages for the hereafter of this is guaranting theta the antibodies can traverse the blood encephalon barriers ( Korth and Peters, 2007 ) .

3. Stoping cofactors that assist in the transition of PrPc to PrPsc ( Korth and Peters, 2007 ) .

4. Using polyanions for illustration Congo dextran which can halt prion protein transition into the mutagenic and infective signifier ( Korth nad Peters, 2007 ) .

5. The cell itself can somehow cut down the sum of PrPsc therefore utilizing excess molecules that enhance this could be a possibility to assist prion diseases, nevertheless the protein which aid with this are still unknown hence farther research should be done to place these proteins ( Korth and Peters, 2007 ) .

6. Stoping the toxic effects that cause seeable symptoms of prion diseases ( Korth and Peters, 2007 ) .

15.1 Drug therapy

Many drugs have been found to be unsuccessful at handling prion diseases, drugs which act against prions can hold toxic effects and many are unable to traverse the blood encephalon barrier ( due to their charged construction ) which is an indispensable belongings to accomplish curative effects as prion diseases are powerful in the encephalon ( Mok et al, 2006 ) .

Drugs that bind cholesterin are known to halt prion protein reproduction and to alter inflammatory reactions ( Mok et al, 2006 ) .

It is utile in drug development to make drugs which are able to work before and after clinical symptoms originate to handle the disease every bit shortly as possible, nevertheless there are no trials to name people with prion diseases before seeable clinical symptoms occur which can do this hard ( Zuber et Al, 2007 ) .

15.1.1 Simvastatin

Simvastatin can be used for therapy of prion diseases and can detain the development of the prion disease which has been shown in an carnal theoretical account ( Mok et al, 2006 ) . Mok et Al ( 2006 ) found that when Zocor was given to mice in vitro they survived on norm up to twenty yearss longer compared to mice given no intervention. However clinical observations were still clear in encephalon countries of both control and mice receiving Zocor ( Mok et al, 2006 ) . Simvastatin was besides found to detain the deadly phase by merely over two hebdomads with no negative affects ( Mok et al, 2009 ) .

To reason Zocor is successful in detaining the age of decease in patients with prion diseases besides take downing cholesterin degrees ( Mok et al, 2009 ) .

However Mok et Al ( 2009 ) have besides tested the consequence of Zocor on mice in vitro, a remaing inquiry is whether the drug work in vivo and even in worlds.

15.1.2 Quinacrine

Quinacrine is a drug used to handle patients with prion diseases, nevertheless has been unsuccessful in increasing the endurance times that patients live ( Ghaemmaghami et al, 2009 ) .

Barret et Al ( 2003 ) tested the effects of mepacrine.

The ability of this drug to do contact with and diminish the sum of PrPsc construct up was tested and besides whether it was able to halt the transition of the prion protein in to the mutated signifier ( Barret et al, 2003 ) .

Barret et Al ( 2003 ) found that Quinacrine was able to adhere with the mutated prion protein nevertheless has no consequence in altering its opposition to protein kinase K.

Barret et Al ( 2003 ) found that Quinacrine was able to halt mutated prion protein formation and was besides able to work through the blood encephalon barrier. However many disadvantages of this drug were found, one chief disadvantage is that it was found to non successfully interrupt already formed protein physique ups ( Barret et al, 2003 ) . Quinacrine was found to be selective in its effects merely in the early phases of the prion disease and was unsuccessful at subsequently phases where clinical symptoms started ( Barret et al,2003 ) .

The chief manner in which worlds are cognizant that they are affected by a prion disease is by noticeable clinical features, hence a drug merely working before the clinical features appear has its disadvantages as intervention normally starts at ulterior phases due to the fact that a prion disease is difficult to observe without clinical symptoms present.

There are no trials that can observe clinical symptoms before the clinical symptoms show ( Zuber et Al, 2007 ) . This can do complications in the development of drugs.

Barret et Al ( 2003 ) found that mepacrine was non effectual in handling human patients enduring from CJD.

Ghaemmaghami et Al ( 2009 ) found that intervention with Quinacrine really consequences in prions that become immune to the effects. They found that intervention with this drug did non increase the clip that mice survived a prion disease ( Ghaemmaghami et al, 2009 ) . It has been proposed that intervention with Quinacrine returns to prion protein that are immune to the drug and survived intervention at the start ( Ghaemmaghami et al, 2009 ) .

Intravenous injection of Quinacrine in to the intellectual ventricle has no increased effectivity on the survival clip of patients ( Ghaemmaghami et al, 2009 ) .

In order to analyze why Quinacrine consequences in prion proteins that become immune Ghaemmaghami et Al ( 2009 ) studied the dynamicss of the prion protein. They found that after intervention with this drug the degrees of the mutated prion protein in the encephalons of septic mice stayed reduced for a few yearss, nevertheless after many yearss the figure of muated prion proteins increased even though the drug was still being taken ( Ghaemmaghami et al, 2009 ) . Ghaemmaghami et Al ( 2009 ) proposed two accounts for this foremost that the marks for the drug in this instance the encephalon alteration the prion proteins response to the drug, secondly that the mutated prion protein becomes able to defy the drug interaction. It has been found that these immune prion proteins merely occur in cells that are non spliting ; hence there is an increased opportunity in cells that are non spliting that the prion proteins that have changed construction survive intervention with Quinacrine ( Ghaemmaghami et al, 2009 ) .

However Ghaemmaghami et Al ( 2009 ) have merely demonstrated the failure of Quinacrine to handle prion diseases in mice, the structural differences in the different signifiers of prion diseases and besides the difference in the different construction of the prion protein in different species could intend that this drug is infact usefull in other instances, farther surveies should be done to tet the effects of Quinacrine treatmentin different species and on different forms/ mutants of teh disease

15.2 Targetting the prion protein receptor

The lamin receptor ( LRP/LR ) has been found as the receptor for the prion protein ( Zuber et Al, 2007 ) .

Therapies have been tested to handle prion diseases affecting the prion protein receptor.

Surveies have found that an LRP mutation is able to diminish mutant priion protein formation in cell affected by scrapie, hence that it may be utile in handling worlds with a prion disease.

RNA break and utilizing antisense engineering can be used in the intervention of prion diseases. The debut of little interfering RNA caused a big loss of mutant prion protein in mice cells affected by the disease ( Zuber et Al, 2007 ) . The initiation of antisense RNA for the lamin receptor consequences in a decreased measure of the receptor and besides stops mutant prion protein patterned advance ( Zuber et Al, 2007 ) .

15.3 Antibody prion therapy

This theapy has been successful in handling malignant neoplastic disease and besides in Alzheimer disease, hence has hope for handling patients with prion diseases ( Tayebi and Hawke, 2006 ) .

The success of this therapy means that reagents need to be established to separate and aim the mutated prion protein ( Tayebi and Hawke, 2006 ) .

Antibody based therapy has been found to do transgenic mice with a prion protein antibody less affected by the mutated prion protein ( Tayebi and Hawke, 2006 ) .

Prolongation of the disease has been found to be successful by the transportation of a recombinant prion protein and peptide ( Tayebi and Hawke, 2006 ) .

Antibodies have besides been affectional in forestalling prion protein reproduction, where animate beings stayed in a healthy status for longer than 600 yearss ( Tayebi and Hawke, 2006 ) .