Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson's disease.
By E. Rocha, Briana R. De Miranda, L. Sanders. Neurobiology of Disease, 2018
667 citations recorded by the source corpus.
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.
Subfields: Neurology, Physiology
View Paper: https://www.semanticscholar.org/paper/b1e343d7a6b80a0b55d00b045334b02312a0a3f7
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In Neurology
Citations in the corpus
- Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction (2023, background): “Several studies, both in vivo and in vitro, showed that α-syn could activate microglia, thus generating a pathological inflammatory stimulus with different intensities of response depending on the α-syn isoforms and PD-related gene mutations [63].”
- Aging and aging-related diseases: from molecular mechanisms to interventions and treatments (2022, background): “In addition to glial cells, fibrillar α-syn increases IL-1β secretion by interacting with TLR2, which is associated with NLRP3 inflammasome activation.(224)”