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

Neurobiol Dis. 2018 Jan;109(Pt B):249-257. doi: 10.1016/j.nbd.2017.04.004. Epub 2017 Apr 8.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / pathology
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*


  • alpha-Synuclein