Title |
Post translational changes to α-synuclein control iron and dopamine trafficking; a concept for neuron vulnerability in Parkinson’s disease
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Published in |
Molecular Neurodegeneration, June 2017
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DOI | 10.1186/s13024-017-0186-8 |
Pubmed ID | |
Authors |
James A. Duce, Bruce X. Wong, Hannah Durham, Jean-Christophe Devedjian, David P. Smith, David Devos |
Abstract |
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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Country | Count | As % |
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United Kingdom | 5 | 83% |
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Demographic breakdown
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Scientists | 2 | 33% |
Science communicators (journalists, bloggers, editors) | 1 | 17% |
Mendeley readers
Geographical breakdown
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Student > Bachelor | 17 | 15% |
Researcher | 14 | 12% |
Student > Master | 13 | 11% |
Student > Doctoral Student | 7 | 6% |
Other | 15 | 13% |
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