Evidence for prion-like mechanisms in several neurodegenerative diseases: potential implications for immunotherapy.
Transmissible spongiform encephalopathies (TSEs) are fatal, untreatable neurodegenerative diseases. While the impact of TSEs on human health is relatively minor, these diseases are having a major influence on how we view, and potentially treat, other more common neurodegenerative disorders. Until recently, TSEs encapsulated a distinct category of neurodegenerative disorder, exclusive in their defining characteristic of infectivity. It now appears that similar mechanisms of self-propagation may underlie other proteinopathies such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. This link is of scientific interest and potential therapeutic importance as this route of self-propagation offers conceptual support and guidance for vaccine development efforts. Specifically, the existence of a pathological, self-promoting isoform offers a rational vaccine target. Here, we review the evidence of prion-like mechanisms within a number of common neurodegenerative disorders and speculate on potential implications and opportunities for vaccine development.
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada S7N 5E3 ; Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada S7N 5E5.
Kristen
K
Marciniuk
Ryan
R
Taschuk
Scott
S
Napper
D000818:Animals; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy*; D018621:PrPC Proteins / Q000276:immunology / Q000378:metabolism; D018620:PrPSc Proteins / Q000276:immunology / Q000378:metabolism; D011328:Prions / Q000276:immunology / Q000472:pathogenicity*
D000939:Epitopes; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions