| Autor: |
James A. Duce, Bruce X. Wong, Hannah Durham, Jean-Christophe Devedjian, David P. Smith, David Devos |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Molecular Neurodegeneration, Vol 12, Iss 1, Pp 1-12 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
1750-1326 |
| DOI: |
10.1186/s13024-017-0186-8 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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