title: Review: Spreading the word: precise animal models and validated methods are vital when evaluating prion-like behaviour of alpha-synuclein.
abstract: Synucleinopathies are characterized by abnormal proteinaceous aggregates, mainly composed of fibrillar α-synuclein (α-syn). It is now believed that α-syn can form small aggregates in a restricted number of cells, that propagate to neighbouring cells and seed aggregation of endogenous α-syn, in a 'prion-like manner'. This process could underlie the stereotypical progression of Lewy bodies described by Braak and colleagues across different stages of Parkinson's disease (PD). This prion-like behaviour of α-syn has been recently investigated in animal models of PD or multiple system atrophy (MSA). These models investigate the cell-to-cell transfer of α-syn seeds, or the induction and spreading of α-syn pathology in transgenic or wild-type rodent brain. In this review, we first outline the involvement of α-syn in Lewy body diseases and MSA, and discuss how 'prion-like' mechanisms can contribute to disease. Thereon, we debate the relevance of animal models used to study prion-like propagation. Finally, we review current main histological methods used to assess α-syn pathology both in animal models and in human samples and their relevance to the disease. Specifically, we discuss using α-syn phosphorylated at serine 129 as a marker of pathology, and the novel methods available that allow for more sensitive detection of early pathology, which has relevance for modelling synucleinopathies.
authors.affiliation: Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, Michigan, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Rey
authors.affiliation: Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, Michigan, USA.
authors.forename: S
authors.initials: S
authors.lastname: George
authors.affiliation: Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, Michigan, USA.
authors.forename: P
authors.initials: P
authors.lastname: Brundin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology*; D019578:Multiple System Atrophy / Q000473:pathology*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Braak staging; Lewy bodies; Parkinson's disease; alpha-synuclein; cell-to-cell transfer; multiple system atrophy; pathology spreading; phosphorylated alpha-synuclein; prion-like; propagation