α-Synuclein aggregation and transmission in Parkinson's disease: a link to mitochondria and lysosome

Sci China Life Sci. 2020 Dec;63(12):1850-1859. doi: 10.1007/s11427-020-1756-9. Epub 2020 Jul 15.

Abstract

The presence of intraneuronal Lewy bodies (LBs) and Lewy neurites (LNs) in the substantia nigra (SN) composed of aggregated α-synuclein (α-syn) has been recognized as a hallmark of pathological changes in Parkinson's disease (PD). Numerous studies have shown that aggregated α-syn is necessary for neurotoxicity. Meanwhile, the mitochondrial and lysosomal dysfunctions are associated with α-syn pathogenicity The hypothesis that α-syn transmission in the human brain contributes to the instigation and progression of PD has provided insights into PD pathology. This review will provide a brief overview of increasing researches that shed light on the relationship of α-syn aggregation with mitochondrial and lysosomal dysfunctions, and highlight recent understanding of α-syn transmission in PD pathology.

Keywords: Lewy pathology; aggregation; lysosome; mitochondria; transmission; α-synuclein.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Communication
  • Humans
  • Lewy Bodies / metabolism
  • Lewy Bodies / pathology
  • Lysosomes / metabolism
  • Lysosomes / pathology*
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Neurons / metabolism
  • Neurons / pathology
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • Protein Aggregation, Pathological / metabolism
  • Protein Aggregation, Pathological / pathology
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / metabolism*

Substances

  • alpha-Synuclein