α-Synuclein misfolding and aggregation: Implications in Parkinson’s disease pathogenesis

Mehra, Surabhi ; Sahay, Shruti ; Maji, Samir K. (2019) α-Synuclein misfolding and aggregation: Implications in Parkinson’s disease pathogenesis Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1867 (10). pp. 890-908. ISSN 15709639

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Official URL: http://doi.org/10.1016/j.bbapap.2019.03.001

Related URL: http://dx.doi.org/10.1016/j.bbapap.2019.03.001

Abstract

α-Synuclein (α-Syn) has been extensively studied for its structural and biophysical properties owing to its pathophysiological role in Parkinson’s disease (PD). Lewy bodies and Lewy neurites are the pathological hallmarks of PD and contain α-Syn aggregates as their major component. It was therefore hypothesized that α-Syn aggregation is actively associated with PD pathogenesis. The central role of α-Syn aggregation in PD is further supported by the identification of point mutations in α-Syn protein associated with rare familial forms of PD. However, the correlation between aggregation propensities of α-Syn mutants and their association with PD phenotype is not straightforward. Recent evidence suggested that oligomers, formed during the initial stages of aggregation, are the potent neurotoxic species causing cell death in PD. However, the heterogeneous and unstable nature of these oligomers limit their detailed characterization. α-Syn fibrils, on the contrary, are shown to be the infectious agents and propagate in a prion-like manner. Although α-Syn is an intrinsically disordered protein, it exhibits remarkable conformational plasticity by adopting a range of structural conformations under different environmental conditions. In this review, we focus on the structural and functional aspects of α-Syn and role of potential factors that may contribute to the underlying mechanism of synucleinopathies. This information will help to identify novel targets and develop specific therapeutic strategies to combat Parkinson’s and other protein aggregation related neurodegenerative diseases.

Item Type:Article
Source:Copyright of this article belongs to Elsevier B.V
Keywords:α-Synuclein;Aggregation;Amyloid;Parkinson’s disease
ID Code:126416
Deposited On:31 Oct 2022 04:03
Last Modified:31 Oct 2022 04:03

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