Post translational changes to α-synuclein control iron and dopamine trafficking; a concept for neuron vulnerability in Parkinson's disease.
Mol Neurodegener
; 12(1): 45, 2017 06 07.
Article
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| MEDLINE
| ID: mdl-28592304
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
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Procesamiento Proteico-Postraduccional
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Alfa-Sinucleína
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Neuronas Dopaminérgicas
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Hierro
Límite:
Animals
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Humans
Idioma:
En
Revista:
Mol Neurodegener
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido