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(The FASEB Journal. 2004;18:637-647.)
© 2004 FASEB

Does {alpha}-synuclein modulate dopaminergic synaptic content and tone at the synapse?

ANITA SIDHU1, CHRISTOPHE WERSINGER and PHILIPPE VERNIER*

Department of Pediatrics, Georgetown University, Washington, D.C., USA; and
* Institut de Neurobiologie Alfred FESSARD, C.N.R.S., 91198 Gif-sur-Yvette cedex, France

1 Correspondence: Laboratory of Molecular Neurochemistry, The Research Building, Room W222, 3970 Reservoir Road, NW, Washington, DC 20007, USA. E-mail: sidhua{at}georgetown.edu

{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.—Sidhu, A., Wersinger, C., Vernier, P. Does {alpha}-synuclein modulate dopaminergic synaptic content and tone at the synapse?


Key Words: dopamine transporter • Parkinson’s disease • synucleopathies • MPTP • neurodegeneration • Lewy bodies




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