Journal
FEBS LETTERS
Volume 565, Issue 1-3, Pages 1-5Publisher
WILEY
DOI: 10.1016/j.febslet.2004.03.063
Keywords
dopamine transporter; alpha-synuclein; Parkinson's disease; synucleinopathies; 1-methyl-4-phenyl-1 2,3,6-tetrahydropyrimidine; neurodegeneration; Lewy bodies
Funding
- NINDS NIH HHS [NS-34914, NS-45326] Funding Source: Medline
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Parkinson's disease (PD) is a slow progressive neurodegenerative disorder. Recent evidence suggests a central role for alpha-synuclein, a protein of unknown function, in the genesis of PD. The phenomenon of selective degeneration of dopaminergic neurons in PD may be linked to the potential toxicity of dopamine itself and aberrations in the processes which regulate dopamine content may underlie the pathogenesis of this disease. Here, we review a vital role of alpha-synuclein in the modulation of dopamine transporter (DAT) function, and describe how disruption of this modulatory process permits increased re-uptake of high levels of intracellular dopamine by DAT, causing profound neurotoxicity. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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