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The Vicious Cycle Between α ‐Synuclein Aggregation and Autophagic‐Lysosomal Dysfunction by Giovanni Bellomo; Silvia Paciotti; Leonardo Gatticchi; Lucilla Parnetti is a Medicine article available to read on EtoBox.

What is The Vicious Cycle Between α ‐Synuclein Aggregation and Autophagic‐Lysosomal Dysfunction about?

The accumulation and misfolding of α-synuclein (α-syn) represent the main pathological hallmark of PD. Overexpression of α-syn and failure of cellular protein degradation systems play a major role in α-syn aggregation. The discovery of PD-associated genes related to the autophagic-lysosomal pathway, such as VPS35, LRRK2, GBA1, SMPD1, GALC, ASAH1, SCARB2, CTSD, CTSB, and GLA, confirms the involvement of cellular clearance systems dysfunction in PD pathogenesis. Of importance, lysosomal enzyme activity is altered both in genetic and sporadic PD. Decreased lysosomal enzymes activities were measured in the same brain regions where α-syn accumulates, suggesting that a crosstalk between α-syn aggregation and autophagic-lysosomal impairment may exist. The understanding of autophagic-lysosomal pathway dysfunctions' role in the pathogenesis and progression of synucleinopathies opened new perspectives for novel possible therapeutic strategies. In this article, the evidences and mechanisms of the reciprocal relation between autophagic-lysosomal pathway impairment and misfolded α-syn aggregation and propagation are reviewed, together with the most promising compounds targeting autophagic-lysos

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Author

Giovanni Bellomo; Silvia Paciotti; Leonardo Gatticchi; Lucilla Parnetti

Published

2019

Language

EN

Field

Medicine (Health Sciences)