Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson's disease.


Journal Article (Review)

Parkinson's disease (PD) is a complex, chronic and progressive neurodegenerative disease. While the etiology of PD is likely multifactorial, the protein α-synuclein is a central component to the pathogenesis of the disease. However, the mechanism by which α-synuclein causes toxicity and contributes to neuronal death remains unclear. Mitochondrial dysfunction is also widely considered to play a major role in the underlying mechanisms contributing to neurodegeneration in PD. This review discusses evidence for the neuropathological role for α-synuclein in the dysfunction of dopamine neurons in PD. We also discuss insights into the structure, localization, and cellular roles for α-synuclein that may influence its aggregation properties, ultimately impacting its pathogenicity, role in lysosomal dysfunction and activation of the neuroimmune response. We further highlight recent evidence linking α-synuclein and mitochondrial dysfunction in neurodegeneration. Identifying the underlying mechanisms responsible for this bi-directional relationship between α-synuclein and mitochondrial dysfunction may provide new insights into the pathophysiology of PD.

Full Text

Duke Authors

Cited Authors

  • Rocha, EM; De Miranda, B; Sanders, LH

Published Date

  • January 2018

Published In

Volume / Issue

  • 109 / Pt B

Start / End Page

  • 249 - 257

PubMed ID

  • 28400134

Pubmed Central ID

  • 28400134

Electronic International Standard Serial Number (EISSN)

  • 1095-953X

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2017.04.004


  • eng

Conference Location

  • United States