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

DUCE, James A, WONG, Bruce X, 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 (1), p. 45.

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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
Additional Information:	** From Europe PMC via Jisc Publications Router. ** Licence for this article: cc by
Uncontrolled Keywords:	Iron, Dopamine, Phosphorylation, Oxidation, Oxidative stress, α-synuclein, Post Translational Modification, Endosomal Trafficking, N-terminal Acetylation
Research Institute, Centre or Group - Does NOT include content added after October 2018:	Biomedical Research Centre
Identification Number:	https://doi.org/10.1186/s13024-017-0186-8
Page Range:	p. 45
SWORD Depositor:	Hilary Ridgway
Depositing User:	Hilary Ridgway
Date Deposited:	11 Jul 2017 09:29
Last Modified:	18 Mar 2021 06:05
URI:	https://shura.shu.ac.uk/id/eprint/16158

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