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

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

Author information

1
Pittsburgh Institute for Neurodegenerative Diseases, Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
2
Pittsburgh Institute for Neurodegenerative Diseases, Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: laurie.sanders@duke.edu.

Abstract

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.

PMID:
28400134
DOI:
10.1016/j.nbd.2017.04.004
[Indexed for MEDLINE]

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