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The Role of α‐Synuclein in Both Neuroprotection and Neurodegeneration
Author(s) -
SIDHU ANITA,
WERSINGER CHRISTOPHE,
MOUSSA CHARBEL EH.,
VERNIER PHILIPPE
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1332.016
Subject(s) - neuroprotection , dopaminergic , neurodegeneration , neuroscience , dopamine , neurotoxicity , parkinson's disease , biology , chemistry , medicine , disease , toxicity , organic chemistry
A bstract : Although α‐synuclein is a central player in the pathophysiology of the dopaminergic neurodegeneration that occurs in Parkinson's disease (PD), emerging results suggest that the fundamental property of the wild‐type form of this protein may be one of neuroprotection, as it can inhibit apoptosis in response to various pro‐apoptotic stimuli. Such properties may be lost by its familial PD‐linked mutations upon alterations in its expression levels or clearance (overexpression of the gene, reduced protein degradation) or following exposure to certain neurotoxins. Moreover, converging observations suggest that a primary function for α‐synuclein in dopaminergic neurons may be the regulation of dopamine content and tone at the synapse. In this paper, we review how, indeed, α‐synuclein regulates both the synthesis of dopamine, its storage into vesicles, its release in the synapse, and its re‐uptake into the dopaminergic neurons. We also show how disruption of these events, and of the neuroprotective effects of α‐synuclein, can initiate the observed neurotoxicity of α‐synuclein in dopaminergic neurons and the genesis of the degenerative processes associated with PD.