Post translational changes to α-synuclein control iron and dopamine trafficking; a concept for neuron vulnerability in Parkinson's disease.

DUCE, James, WONG, Bruce, DURHAM, Hannah, DEVEDJIAN, Jean-Christophe, SMITH, David and DEVOS, David (2017). Post translational changes to α-synuclein control iron and dopamine trafficking; a concept for neuron vulnerability in Parkinson's disease. Molecular neurodegeneration, 12 (45), 1-12.

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Link to published version:: 10.1186/s13024-017-0186-8

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.

Item Type: Article
Uncontrolled Keywords: α-synuclein, Iron, Dopamine, Endosomal trafficking, Oxidative stress, Post translational modification, N-terminal acetylation, Phosphorylation, Oxidation
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Departments: Health and Well-being > Bioscience
Identification Number: 10.1186/s13024-017-0186-8
Depositing User: David Smith
Date Deposited: 11 Oct 2017 10:25
Last Modified: 11 Oct 2017 10:28
URI: http://shura.shu.ac.uk/id/eprint/16956

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