Post translational changes to alpha-synuclein control iron and dopamine trafficking; a concept for neuron vulnerability in Parkinson's disease
Web of Science
AuthorDuce, JA; Wong, BX; Durham, H; Devedjian, J-C; Smith, DP; Devos, D
Source TitleMolecular Neurodegeneration
AffiliationFlorey Department of Neuroscience and Mental Health
Biochemistry and Molecular Biology
Document TypeJournal Article
CitationsDuce, J. A., Wong, B. X., Durham, H., Devedjian, J. -C., Smith, D. P. & Devos, D. (2017). Post translational changes to alpha-synuclein control iron and dopamine trafficking; a concept for neuron vulnerability in Parkinson's disease. MOLECULAR NEURODEGENERATION, 12 (1), https://doi.org/10.1186/s13024-017-0186-8.
Access StatusOpen Access
Parkinson's disease is a multifactorial neurodegenerative disorder, the aetiology of which remains elusive. The primary clinical feature of progressively impaired motor control is caused by a loss of midbrain substantia nigra dopamine neurons that have a high α-synuclein (α-syn) and iron content. α-Syn is a neuronal protein that is highly modified post-translationally and central to the Lewy body neuropathology of the disease. This review provides an overview of findings on the role post translational modifications to α-syn have in membrane binding and intracellular vesicle trafficking. Furthermore, we propose a concept in which acetylation and phosphorylation of α-syn modulate endocytic import of iron and vesicle transport of dopamine during normal physiology. Disregulated phosphorylation and oxidation of α-syn mediate iron and dopamine dependent oxidative stress through impaired cellular location and increase propensity for α-syn aggregation. The proposition highlights a connection between α-syn, iron and dopamine, three pathological components associated with disease progression in sporadic Parkinson's disease.
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