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Article Dans Une Revue Annals of the New York Academy of Sciences Année : 2004

The Role of α-Synuclein in Both Neuroprotection and Neurodegeneration.

Résumé

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.

Dates et versions

hal-00018374 , version 1 (01-02-2006)

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Citer

Anita Sidhu, Christophe Wersinger, E.-H. Moussa Charbel, Philippe Vernier. The Role of α-Synuclein in Both Neuroprotection and Neurodegeneration.. Annals of the New York Academy of Sciences, 2004, 1035, pp.250. ⟨10.1196/annals.1332.016⟩. ⟨hal-00018374⟩

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