Journal
FASEB JOURNAL
Volume 18, Issue 6, Pages 637-647Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.03-1112rev
Keywords
dopamine transporter; Parkinson's disease; synucleopathies; neurodegeneration; MPTP; Lewy bodies
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Funding
- NINDS NIH HHS [NS-34914, NS-45326] Funding Source: Medline
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Alpha-Synuclein is a key component of the pathological process of neurodegeneration in Parkinson's disease. Although its contributions to normal physiological conditions remain elusive, converging observations suggest that a primary function of this protein in dopaminergic neurons may be the regulation of dopamine content and synaptic tone at the synapse. We review here cumulative evidence that demonstrates the participation of alpha-synuclein in the life cycle of dopamine from its synthesis, storage, release, and reuptake. The regulatory role of alpha-synuclein on dopamine metabolism is assessed by discussing the experimental evidence supporting each of these observations in the healthy physiological maintenance of dopaminergic neurons, as well as showing how disruption of these events can initiate the observed neurotoxicity of alpha-synuclein and the genesis of the degenerative processes associated with Parkinson's disease.
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