Review
Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a 
Prion-Like Disorder? 
C. Warren Olanow MD1,*, Patrik Brundin MD, PhD2,3 
Article first published online: 6 FEB 2013
DOI: 10.1002/mds.25373
Copyright © 2013 Movement Disorder Society 
Additional Information(Hide All) How to CiteAuthor InformationPublication 
History How to Cite Olanow, C. W. and Brundin, P. (2013), Parkinson's Disease 
and Alpha Synuclein: Is Parkinson's Disease a Prion-Like Disorder?. Mov. 
Disord., 28: 31–40. doi: 10.1002/mds.25373
Author Information 1 Departments of Neurology and Neuroscience, Mount Sinai 
School of Medicine, New York, New York, USA 2 Van Andel Research Institute, 
Center for Neurodegenerative Science, Grand Rapids, Michigan, USA 3 Neuronal 
Survival Unit, BMC B11, Department of Experimental Medical Science, Wallenberg 
Neuroscience Center, Lund University, Lund, Sweden *Correspondence to: Dr. C. 
Warren Olanow, Department of Neurology, Mount Sinai School of Medicine, 
Annenberg 20–92, One Gustave L. Levy Place, Box 1137, New York, NY 10029; warren.olanow@mssm.edu
Relevant conflicts of interest/financial disclosures: Nothing to 
report.
Full financial disclosures and author roles may be found in the online 
version of this article.
Publication History Issue published online: 6 FEB 2013 Article first 
published online: 6 FEB 2013 Manuscript Accepted: 2 JAN 2013 Manuscript 
Received: 26 DEC 2012 
Keywords:misfolded α-synuclein;β-sheet formation;Lewy-like 
pathology;prions;toxic oligomers
ABSTRACT 
Altered protein handling is thought to play a key role in the 
etiopathogenesis of Parkinson's disease (PD), as the disorder is characterized 
neuropathologically by the accumulation of intraneuronal protein aggregates 
(Lewy bodies and Lewy neurites). Attention has particularly focused on the 
α-synuclein protein, as it is the principal component of Lewy pathology. 
Moreover, point mutations in the α-synuclein gene cause rare familial forms of 
PD. Importantly, duplication/triplication of the wild type α-synuclein gene also 
cause a form of PD, indicating that increased levels of the normal α-synuclein 
protein is sufficient to cause the disease. Further, single nucleotide 
polymorphisms in the α-synuclein gene are associated with an increased risk of 
developing sporadic PD. Recent evidence now suggests the possibility that 
α-synuclein is a prion-like protein and that PD is a prion-like disease. Within 
cells, α-synuclein normally adopts an α-helical conformation. However, under 
certain circumstances, the protein can undergo a profound conformational 
transition to a β-sheet–rich structure that polymerizes to form toxic oligomers 
and amyloid plaques. Recent autopsy studies of patients with advanced PD who 
received transplantation of fetal nigral mesencephalic cells more than a decade 
earlier demonstrated that typical Lewy pathology had developed within grafted 
neurons. This suggests that α-synuclein in an aberrantly folded, β-sheet–rich 
form had migrated from affected to unaffected neurons. Laboratory studies 
confirm that α-synuclein can transfer from affected to unaffected nerve cells, 
where it appears that the misfolded protein can act as a template to promote 
misfolding of host α-synuclein. This leads to the formation of larger 
aggregates, neuronal dysfunction, and neurodegeneration. Indeed, recent reports 
demonstrate that a single intracerebral inoculation of misfolded α-synuclein can 
induce Lewy-like pathology in cells that can spread from affected to unaffected 
regions and can induce neurodegeneration with motor disturbances in both 
transgenic and normal mice. Further, inoculates derived from the brains of 
elderly α-synuclein–overexpressing transgenic mice have now been shown to 
accelerate the disease process when injected into the brains of young transgenic 
animals. Collectively, these findings support the hypothesis that α-synuclein is 
a prion-like protein that can adopt a self-propagating conformation that causes 
neurodegeneration. We propose that this mechanism plays an important role in the 
development of PD and provides novel targets for candidate neuroprotective 
therapies. © 2013 Movement Disorder Society 
Sunday, December 9, 2012
Prions, prionoids and pathogenic proteins in Alzheimer disease 
Mini-Review 
Wednesday, September 21, 2011 
PrioNet Canada researchers in Vancouver confirm prion-like properties in 
Amyotrophic 
Lateral Sclerosis (ALS) 
Researchers’ Discovery May Revolutionize Treatment of ALS
PrioNet Canada researchers in Vancouver confirm prion-like properties in 
Amyotrophic Lateral Sclerosis (ALS)
September 20, 2011 (Vancouver, BC) - A team of researchers from the 
University of British Columbia and the Vancouver Coastal Health Research 
Institute have found a key link between prions and the neurodegenerative disease 
ALS (Amyotrophic Lateral Sclerosis), also known as Lou Gehrig’s disease. The 
discovery is significant as it opens the door to novel approaches to the 
treatment of ALS.
A pivotal paper published by the team this week in the Proceedings of the 
National Academy of Sciences (PNAS), demonstrates that the SOD1 protein 
(superoxide dismutase 1), which has been shown to be implicated in the ALS 
disease process, exhibits prion-like properties. The researchers found that SOD1 
participates in a process called template-directed misfolding. This term refers 
to the coercion of one protein by another protein to change shape and accumulate 
in large complexes in a fashion similar to the process underlying prion 
diseases.
These findings provide a molecular explanation for the progressive spread 
of ALS through the nervous system, and highlight the central role of the 
propagation of misfolded proteins in the pathogenesis of neurodegenerative 
diseases, including ALS, Alzheimer’s and Parkinson’s.
“Our work has identified a specific molecular target, which when 
manipulated halts the conversion of the SOD1 protein to a misfolded, 
disease-causing form,” says Dr. Neil Cashman, Scientific Director of PrioNet 
Canada, Canada Research Chair in Neurodegeneration and Protein Misfolding at 
UBC, and academic director of the Vancouver Coastal Health ALS Centre. “This 
discovery is a first-step toward the development of targeted treatments that may 
stop progression of ALS.”
ALS is a progressive neuromuscular disease in which nerve cells die, 
resulting in paralysis and death. Approximately 2,500 to 3,000 Canadians 
currently live with this fatal disease, for which there is no effective 
treatment yet.
“For many years, ALS has remained a complex puzzle and we have found a key 
piece to help guide the research community to solutions,” says Dr. Leslie Grad, 
a co-first author of the project and current Manager of Scientific Programs at 
PrioNet Canada. “PrioNet is further exploring this discovery through 
newly-funded research projects.”
The work was completed by Dr. Neil Cashman’s lab at the Brain Research 
Centre based at the University of British Columbia and the Vancouver Coastal 
Health Research Institute, in collaboration with researchers at the University 
of Alberta. The research was supported by PrioNet Canada and in part by Amorfix 
Life Sciences and the Canadian Institutes of Health Research.
PrioNet Canada, based in Vancouver, has achieved international attention 
for scientific discoveries and risk management strategies directed at 
controlling prion diseases, and is now directing capacity into therapeutic 
solutions for prion-like diseases of aging, such as Alzheimer’s, Parkinson’s and 
ALS.
About: One of Canada’s Networks of Centres of Excellence, PrioNet Canada 
(www.prionetcanada.ca) is developing strategies to help solve the food, health 
safety, and socioeconomic problems associated with prion diseases. The network 
brings together scientists, industry, and public sector partners through its 
multidisciplinary research projects, training programs, events, and 
commercialization activities. PrioNet is hosted by the University of British 
Columbia and the Vancouver Coastal Health Research Institute in Vancouver.
The University of British Columbia (UBC) is one of North America’s largest 
public research and teaching institutions, and one of only two Canadian 
institutions consistently ranked among the world’s 40 best universities. UBC is 
a place that inspires bold, new ways of thinking that have helped make it a 
national leader in areas as diverse as community service learning, 
sustainability and research commercialization. UBC offers more than 50,000 
students a range of innovative programs and attracts $550 million per year in 
research funding from government, non-profit organizations and industry through 
7,000 grants.
Vancouver Coastal Health Research Institute (VCHRI) (www.vchri.ca) is the 
research body of Vancouver Coastal Health Authority, which includes BC’s largest 
academic and teaching health sciences centres: VGH, UBC Hospital, and GF Strong 
Rehabilitation Centre. In academic partnership with the University of British 
Columbia, VCHRI brings innovation and discovery to patient care, advancing 
healthier lives in healthy communities across British Columbia, Canada, and 
beyond.
The Brain Research Centre comprises more than 200 investigators with 
multidisciplinary expertise in neuroscience research ranging from the test tube, 
to the bedside, to industrial spin-offs. The centre is a partnership of UBC and 
Vancouver Coastal Health Research Institute. For more information, visit www.brain.ubc.ca.
- 30 -
Media information or to set up interviews: Gail Bergman, Gail Bergman PR 
Tel: (905) 886-1340 or (905) 886-3345 E-mail: info@gailbergmanpr.com
Backgrounder - ALS as a "prion-like" disease
Amyotrophic lateral sclerosis (ALS): Amyotrophic lateral sclerosis (ALS), 
also known as Lou Gehrig ’s disease in the United States and motor neurone 
disease (MND) in Europe, is a fatal neurodegenerative disease caused by 
deterioration of motor neurons in the brain and spinal cord. Individuals living 
with the disease experience progressive paralysis, as well as difficulty 
breathing or swallowing. At this time, no cure or effective treatment 
exists.
According to the ALS Society of Canada: • ALS is the most common cause of 
neurological death • Every day two or three Canadians die of ALS • Eighty per 
cent of people with ALS die within two to five years of diagnosis; ten per cent 
of those affected may live for 10 years or longer • Approximately 2,500 - 3,000 
Canadians currently live with this fatal disease • The World Health Organization 
predicts that neurodegenerative diseases will surpass cancer as the second 
leading cause of death in Canada by 2040
Background: Recent research highlights links between the biological 
mechanisms of common neurological disorders, such as ALS, Alzheimer’s and 
Parkinson’s disease with prion disease. While each of these diseases manifests 
itself in a different way, the hallmark of each is a progressive accumulation of 
misfolded protein aggregates in the central nervous system.
Correctly-folded proteins adopt one particular structure in order to carry 
out their intended function. A protein’s failure to adopt this correct structure 
is what threatens the health of cells. Prions are “misfolded” proteins -- the 
infectious, aggregating agents in diseases such as Creutzfeldt-Jakob disease 
(CJD) in humans, chronic wasting disease (CWD) in deer and elk and bovine 
spongiform encephalopathy (BSE), also known as “mad cow” disease in cattle. In 
ALS, Alzheimer’s and Parkinson’s, the misfolded proteins are SOD1, amyloid-ß, 
and a-synuclein, respectively.
Key Finding: “Intermolecular transmission of SOD-1 misfolding in living 
cells” - Published in the Proceedings of the National Academy of Sciences 
(PNAS), September 2011 • The paper shows that superoxide dismutase 1 (SOD1) 
participates in template-directed misfolding, in other words, the coercion of 
one protein by another protein to change shape and aggregate such as prion 
diseases do. • The results will be significant to the ALS field because it 
connects prion mechanisms behind the biological progression of ALS, and provides 
a molecular explanation for the linear and temporal spread of ALS through the 
nervous system. • Furthermore, the research has identified a specific molecular 
target, which when manipulated, halts the conversion of SOD1 to a misfolded, 
disease-causing form. This is a first-step towards the development of targeted 
treatments that may stop ALS, which PrioNet is further exploiting through 
newly-funded research. • This research was supported by PrioNet Canada and in 
part by Amorfix Life Sciences and the Canadian Institutes of Health 
Research.
Other Research: Studies showing how “seed” misfolded protein induce 
aggregation of other protein, which provide evidence for prion-like spread: • 
Lary Walker’s group at Emory University in Atlanta, in collaboration with 
Matthias Jucker and others at the Universities of Tübingen in Germany and Basel 
in Switzerland, discovered that aggregates of amyloid-ß protein from the brain 
of people with Alzheimer’s disease could be transmitted to the brain of healthy 
mice. • Another study by Patrik Brundin’s group in Sweden demonstrated that 
healthy tissue surgically implanted into the brain of people with Parkinson’s 
disease acquired the aggregates of a-synuclein protein characteristic of the 
disease. • Eliezer Masliah of the University of California San Diego and others 
discovered that aggregates of a-synuclein can travel from cell to cell, forming 
the aggregates in human neurons that are characteristic of Parkinson’s disease 
and certain types of dementia. • Anne Bertolotti from the University of 
Cambridge discovered that neuronal cells spontaneously and efficiently take up 
misfolded mutant SOD1 from their environment. The internalized mutant SOD1 
triggers a change in shape of the normally soluble mutant SOD1 protein, which 
causes its aggregation, and is then transferred to neighbouring cells in a 
prion-like fashion.
Last Updated: 9/20/2011 3:19:45 PM
posted: 9/20/2011 
snip...see full test ; 
Are some commoner types of neurodegenerative disease (including Alzheimer's 
disease and Parkinson's disease) also transmissible? Some recent scientific 
research has suggested this possibility. 
Friday, September 3, 2010.
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, 
Prionpathy, Prionopathy, TSE. 
Wednesday, September 21, 2011. 
PrioNet Canada researchers in Vancouver confirm prion-like properties in 
Amyotrophic Lateral Sclerosis (ALS). 
Wednesday, January 5, 2011. 
... ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 
Prions. 
David W. Colby1,* and Stanley B. Prusiner1,2 
Saturday, January 22, 2011
Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there 
of, a review 2011
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, 
Prionpathy, Prionopathy, TSE
Sunday, August 8, 2010
The Transcellular Spread of Cytosolic Amyloids, Prions, and Prionoids
Are some commoner types of neurodegenerative disease (including Alzheimer's 
disease and Parkinson's disease) also transmissible? Some recent scientific 
research has suggested this possibility
Monday, October 12, 2009
SEAC Science and Technology Committee's investigation of research funding 
priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 
October 2009
see full text and more science on this topic here ; 
13
Simultaneous Onset of Alzheimer's Disease in a Husband and Wife in Their 
Mid Fifties: What do We Really Know? 
Jonathan Heath1, Lindsay Goicochea2, Mark Smith3, Rudy Castellani4. 
1Department of Pathology, University of Maryland; 2University; 3Case Western 
Reserve University; 4University of Maryland, Baltimore, Maryland
Whereas the genetic factors influencing the development and expression of 
Alzheimer's disease are well characterized, environmental factors are currently 
thought to play a marginal role. Such factors as prior closed head injury, 
post-menopausal estrogen deficiency, aluminum exposure, smoking, diabetes, 
atherosclerotic cardiovascular disease, and diet, among others, confer only a 
modest increased risk if any, and are only tangentially considered in the major 
pathogenic cascades that are presently hypothesized. We present the simultaneous 
onset of Alzheimer's disease in a husband and wife, with both subjects 
experiencing cognitive dysfunction within the same month. Both subjects were in 
their mid-fifties at the time of presentation, both subjects showed 
progressively neurological decline with prominent memory loss, both subjects 
experienced myoclonus late in their disease course prompting referral to the 
National Prion Disease Pathology Surveillance Center, and both subjects expired 
12 years after onset, within two months of each other. Review of the family 
pedigree revealed no family history of dementia or other neurologic illnesses in 
multiple first degree relatives. The only historical finding of note was that 
both subjects had moved out of their home briefly while it was being remodeled, 
and both became symptomatic shortly after moving back in. At autopsy, the 
subjects had classic advanced Alzheimer's disease, with Braak stage VI pathology 
that was otherwise identiical in quantity and distribution of amyloid-beta, 
cerebral amyloid angiopathy, and neurofibrillary degeneration. While no specific 
toxin or other environmental cause was discerned, these two cases raise the 
issue of epigenetic factors in Alzheimer's disease that may be more robust than 
current literature indicates.
NEUROLOGY 1998;50:684-688 © 1998 American Academy of Neurology
Creutzfeldt-Jakob disease in a husband and wife
P. Brown, MD, L. Cervenáková, MD, L. McShane, PhD, L. G. Goldfarb, MD, K. 
Bishop, BS, F. Bastian, MD, J. Kirkpatrick, MD, P. Piccardo, MD, B. Ghetti, MD 
and D. C. Gajdusek, MD From the Laboratory of CNS Studies (Drs. Brown, 
Cervenáková, Goldfarb, and Gajdusek), NINDS, and Biometric Research Branch (Dr. 
McShane), NCI, National Institutes of Health, Bethesda, MD; the Department of 
Obstetrics (K. Bishop), Gynecology and Reproductive Sciences, University of 
Texas Houston Health Science Center, Houston, TX; the Department of Pathology 
(Dr. Bastian), University of South Alabama Medical Center, Mobile, AL; the 
Department of Pathology (Dr. Kirkpatrick), The Methodist Hospital, Houston, TX; 
and the Department of Pathology (Drs. Piccardo and Ghetti), Indiana University 
School of Medicine, Indianapolis, IN.
Address correspondence and reprint requests to Dr. Paul Brown, Building 36, 
Room 5B21, National Institutes of Health, Bethesda, MD 20892.
A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a 
1.5-year clinical course. Four and a half years later, his then 55-year-old 
widow died from CJD after a 1-month illness. Both patients had typical clinical 
and neuropathologic features of the disease, and pathognomonic 
proteinase-resistant amyloid protein ("prion" protein, or PrP) was present in 
both brains. Neither patient had a family history of neurologic disease, and 
molecular genetic analysis of their PrP genes was normal. No medical, surgical, 
or dietary antecedent of CJD was identified; therefore, we are left with the 
unanswerable alternatives of human-to-human transmission or the chance 
occurrence of sporadic CJD in a husband and wife.
--------------------------------------------------------------------------------
Received May 5, 1997. Accepted in final form September 10, 1997.
Research Lead: Dr. David Westaway, University of Alberta
Project: "Extending the spectrum of Prionopathies to Amyotrophic Lateral 
Sclerosis and Autism"
This project proposes to link the chemistry of the prion protein to the new 
territory of other nervous system diseases, such as ALS (Lou Gehrig's disease) 
and the socialization disorder autism-diseases which are at least one thousand 
times more common than prion diseases. It is believed that a different type or 
prion protein may operate in other types of brain diseases, which could lead to 
new ways of thinking about incurable disorders. The project will create changes 
in the amounts of the various forms of the new membrane protein, and then 
perform an array of analyses on the behavior and nervous system transmission of 
laboratory mice. Nervous transmission by electrical impulse can be measured in 
isolated brain cells, a system that is also convenient to study the effect of 
stress by adding small amounts of toxins to the fluids bathing the cultures. By 
these means, the project aims to extend the boundaries of what is considered 
"prion disease."
Funding: $520,500
Unfolding the Prion Mystery Building and Growing Research Expertise in 
Alberta Year 4 2008-2009 Annual Report
Dr. David Westaway, University of Alberta Extending the spectrum of 
prionopathies to amyotrophic lateral sclerosis (ALS) and autism Dr. Westaway’s 
study aims to extend the boundaries of what is considered prion disease. His 
project takes the chemistry of the prion protein into the territory of nervous 
system diseases such as ALS (Lou Gehrig’s disease) and socialization disorder 
diseases such as autism. These brain diseases are at least 1,000 times more 
common than diseases currently accepted as prion related. Dr. Westaway 
hypothesizes that a different type of protein misfolding may operate in brain 
diseases such as Lou Gehrig’s and autism. This type of protein misfolding may 
occur in response to stresses in the brain. Unlike misfolded prions, other 
misfolded proteins may be noninfectious and not viable outside of the affected 
animal. Dr. Westaway’s research team will investigate these hypotheses by 
inducing changes in the brain cells of laboratory mice, measuring the resulting 
electrical impulses in the animals’ nervous systems and analyzing the effect on 
behaviour. Because nervous transmission by electrical impulse can be measured in 
isolated brain cells, adding small amounts of toxins to the fluids bathing the 
cell cultures will make it possible to study the effect of stress. The results 
could lead to new ways of thinking about nervous system disorders.
Published Date: 2011-10-03 19:22:21 
Subject: PRO/AH/EDR> Prion disease update 2011 (09) Archive Number: 
20111003.2983
PRION DISEASE UPDATE 2011 (09) 
****************************** 
snip... 
****** 
[6] 
ALS a prion disease 
Date: Tue 20 Sep 2011 
Source: PrioNet Canada [abridged & edited] 
A team of researchers from the University of British Columbia (BC) and the 
Vancouver Coastal Health Research Institute have found a key link between prions 
and the neurodegenerative disease ALS (Amyotrophic Lateral Sclerosis), also 
known as Lou Gehrig's disease. The discovery is significant as it opens the door 
to novel approaches to the treatment of ALS.
A pivotal paper published by the team this week in the Proceedings of the 
National Academy of Sciences (PNAS), demonstrates that the SOD1 protein 
(superoxide dismutase 1), which has been shown to be implicated in the ALS 
disease process, exhibits prion-like properties. The researchers found that SOD1 
participates in a process called template-directed misfolding. This term refers 
to the coercion of one protein by another protein to change shape and accumulate 
in large complexes in a fashion similar to the process underlying prion 
diseases.
These findings provide a molecular explanation for the progressive spread 
of ALS through the nervous system, and highlight the central role of the 
propagation of misfolded proteins in the pathogenesis of neurodegenerative 
diseases, including ALS, Alzheimer's and Parkinson's.
"Our work has identified a specific molecular target, which when 
manipulated halts the conversion of the SOD1 protein to a misfolded, 
disease-causing form," says Dr. Neil Cashman, Scientific Director of PrioNet 
Canada, Canada Research Chair in Neurodegeneration and Protein Misfolding at 
UBC, and academic director of the Vancouver Coastal Health ALS Centre. "This 
discovery is a 1st-step toward the development of targeted treatments that may 
stop progression of ALS."
ALS is a progressive neuromuscular disease in which nerve cells die, 
resulting in paralysis and death. Approximately 500 to 3000 Canadians currently 
live with this fatal disease, for which there is no effective treatment 
yet.
"For many years, ALS has remained a complex puzzle, and we have found a key 
piece to help guide the research community to solutions," says Dr. Leslie Grad, 
a co-1st author of the project and current Manager of Scientific Programs at 
PrioNet Canada. "PrioNet is further exploring this discovery through 
newly-funded research projects."
The work was completed by Dr. Neil Cashman's lab at the Brain Research 
Centre based at the University of British Columbia and the Vancouver Coastal 
Health Research Institute, in collaboration with researchers at the University 
of Alberta. The research was supported by PrioNet Canada and in part by Amorfix 
Life Sciences and the Canadian Institutes of Health Research.
PrioNet Canada, based in Vancouver, has achieved international attention 
for scientific discoveries and risk management strategies directed at 
controlling prion diseases and is now directing capacity into therapeutic 
solutions for prion-like diseases of aging, such as Alzheimer's, Parkinson's and 
ALS.
[The paper referred to in the preceding press release above is entitled: 
Intermolecular transmission of superoxide dismutase 1 misfolding in living 
cells, by Leslie I. Grada and 9 others, Published in the Proceedings of the 
Academy of Sciences online before print in 19 Sept 2011, 
doi:10.1073/pnas.1102645108 http://www.pnas.org/content/early/2011/09/13/1102645108.abstract. 
The Abstract reads as follows: "Human wild-type superoxide dismutase-1 
(wtSOD1) is known to coaggregate with mutant SOD1 in familial amyotrophic 
lateral sclerosis (FALS), in double transgenic models of FALS, and in cell 
culture systems, but the structural determinants of this process are unclear. 
Here we molecularly dissect the effects of intracellular and cell-free 
obligately misfolded SOD1 mutant proteins on natively structured wild-type SOD1. 
Expression of the enzymatically inactive, natural familial ALS SOD1 mutations 
G127X and G85R in human mesenchymal and neural cell lines induces misfolding of 
wild-type natively structured SOD1, as indicated by: acquisition of 
immunoreactivity with SOD1 misfolding-specific monoclonal antibodies; markedly 
enhanced protease sensitivity suggestive of structural loosening; and nonnative 
disulfide-linked oligomer and multimer formation. Expression of G127X and G85R 
in mouse cell lines did not induce misfolding of murine wtSOD1, and a species 
restriction element for human wtSOD1 conversion was mapped to a region of 
sequence divergence in loop II and beta-strand 3 of the SOD1 beta-barrel 
(residues 24-36), then further refined surprisingly to a single tryptophan 
residue at codon 32 (W32) in human SOD1. Time course experiments enabled by W32 
restriction revealed that G127X and misfolded wtSOD1 can induce misfolding of 
cell-endogenous wtSOD1. Finally, aggregated recombinant G127X is capable of 
inducing misfolding and protease sensitivity of recombinant human wtSOD1 in a 
cell-free system containing reducing and chelating agents; cell-free wtSOD1 
conversion was also restricted by W32. These observations demonstrate that 
misfolded SOD1 can induce misfolding of natively structured wtSOD1 in a 
physiological intracellular milieu, consistent with a direct protein-protein 
interaction." 
-- Communicated by: Terry S. Singeltary Sr. flounder9@verizon.net 
[Prions are "misfolded" proteins, the infectious, aggregating agents in 
diseases such as Creutzfeldt-Jakob disease (CJD) in humans, chronic wasting 
disease (CWD) in deer and elk and bovine spongiform encephalopathy (BSE), also 
known as "mad cow‚" disease in cattle. In ALS, Alzheimer's and Parkinson's, the 
misfolded proteins are SOD1, beta-amyloid, and alpha-synuclein, 
respectively.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig 's disease in 
the United States and motor neuron disease (MND) in Europe, is a fatal 
neurodegenerative disease caused by deterioration of motor neurons in the brain 
and spinal cord. Individuals living with the disease experience progressive 
paralysis, as well as difficulty breathing or swallowing. At this time, no cure 
or effective treatment exists.
Recent research highlights links between the biological mechanisms of 
common neurological disorders, such as ALS, Alzheimer's and Parkinson's disease 
with prion disease. While each of these diseases manifests itself in a different 
way, the hallmark of each is a progressive accumulation of misfolded protein 
aggregates in the central nervous system. - Mod.CP] 
Tuesday, October 4, 2011 
Alzheimer's disease is a Transmissible Spongiform Encephalopathy Prion 
disease 
Molecular Psychiatry advance online publication 4 October 2011; doi: 
10.1038/mp.2011.120 
SCENARIO 4: ‘WE HAD OUR CHANCE AND WE BLEW IT’.
Unsustainable Production and Robust Markets. 
Canada
Science
- Experimental evidence indicates that abnormal prions may persist for 
undetermined periods of time in buried materials.
- A new prion disease has occurred in cattle, possibly originated from CWD. 
Research funds are not available to investigate its nature and origin.
- The origin, transmission and prevalence of atypical BSE remain 
unclear.
- L-type atypical BSE has been demonstrated to be transmissible to 
humans.
- New testing procedures indicate the presence of sub-clinical carriers in 
the cattle population.
- New scientific knowledge provides no evidence that CWD is transmissible 
from Cervids to humans. 
SNIP...SEE FULL TEXT ;. 
Sunday, December 2, 2012. 
CANADA 19 cases of mad cow disease SCENARIO 4: ‘WE HAD OUR CHANCE AND WE 
BLEW IT’.
Wednesday, May 16, 2012. 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion 
disease, Iatrogenic, what if? 
Proposal ID: 29403. 
TSS 

 
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