期刊
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
卷 42, 期 1, 页码 51-76出版社
WILEY
DOI: 10.1111/nan.12299
关键词
Parkinson's disease; multiple system atrophy; Lewy bodies; alpha-synuclein; prion-like; propagation; pathology spreading; cell-to-cell transfer; Braak staging; phosphorylated alpha-synuclein
资金
- Van Andel Institute
- Peter C. and Emajean Cook Foundation
- Michael J Fox Foundation USA
- National Institutes of Health
- Cure Parkinson's Trust
- TEVA Neuroscience
- East Tennessee Fdn KiMe Foundation
- Campbell Foundation
Synucleinopathies are characterized by abnormal proteinaceous aggregates, mainly composed of fibrillar -synuclein (-syn). It is now believed that -syn can form small aggregates in a restricted number of cells, that propagate to neighbouring cells and seed aggregation of endogenous -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 -syn has been recently investigated in animal models of PD or multiple system atrophy (MSA). These models investigate the cell-to-cell transfer of -syn seeds, or the induction and spreading of -syn pathology in transgenic or wild-type rodent brain. In this review, we first outline the involvement of -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 -syn pathology both in animal models and in human samples and their relevance to the disease. Specifically, we discuss using -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.
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