Title :

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

Author(s) :

Duce, James A. [Auteur]
Wong, Bruce X. [Auteur]
Durham, Hannah [Auteur]
Devedjian, Jean-Christophe [Auteur]
Smith, David P. [Auteur]
DEVOS, DAVID [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Troubles cognitifs dégénératifs et vasculaires - U1171
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]

Journal title :

Molecular neurodegeneration

Abbreviated title :

Mol. Neurodegener.

Volume number :

12

Publication date :

2017-06-07

ISSN :

1750-1326

English keyword(s) :

Iron
alpha-synuclein
Oxidation
Phosphorylation
N-terminal acetylation
Post translational modification
Endosomal trafficking
Oxidative stress
Dopamine

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
CNRS
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Troubles cognitifs dégénératifs et vasculaires

Submission date :

2019-11-27T13:04:13Z