title: The prion hypothesis in Parkinson's disease: Braak to the future.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder typified by the presence of intraneuronal inclusions containing aggregated alpha synuclein (αsyn). The progression of parkinsonian pathology and clinical phenotype has been broadly demonstrated to follow a specific pattern, most notably described by Braak and colleagues. In more recent times it has been hypothesized that αsyn itself may be a critical factor in mediating transmission of disease pathology from one brain area to another. Here we investigate the growing body of evidence demonstrating the ability of αsyn to spread transcellularly and induce pathological aggregation affecting neurons by permissive templating and provide a critical analysis of some irregularities in the hypothesis that the progression of PD pathology may be mediated by such a prion-like process. Finally we discuss some key questions that remain unanswered which are vital to determining the potential contribution of a prion-like process to the pathogenesis of PD.
authors.affiliation: Division of Patient Based Clinical Research, Toronto Western Research Institute, and the Edmond J, Safra Program in Parkinson's Disease, Toronto Western Hospital, McLaughlin Pavilion, 7th Floor Rm 7-403, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. lang@uhnres.utoronto.ca.
authors.forename: Naomi P
authors.initials: NP
authors.lastname: Visanji
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Brooks
authors.forename: Lili-Naz
authors.initials: LN
authors.lastname: Hazrati
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
mesh_terms: D000818:Animals; D006801:Humans; D008959:Models, Neurological; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D011328:Prions / Q000502:physiology*; D012720:Severity of Illness Index
chemical_list: D011328:Prions