α-Synuclein and dopamine at the crossroads of Parkinson's disease.

Venda LL., Cragg SJ., Buchman VL., Wade-Martins R.

α-Synuclein is central to the Lewy body neuropathology of Parkinson's disease (PD), a devastating neurodegenerative disorder characterized by numerous motor and non-motor manifestations. The cardinal motor symptoms are linked to death of dopaminergic neurons in the nigrostriatal pathway. Here we ask why these neurons are preferentially susceptible to neurodegeneration in PD and how α-synuclein is involved. To address these questions we bring together recent findings from genome-wide association studies, which reveal the involvement of α-synuclein gene variants in sporadic PD, with recent studies highlighting important roles for α-synuclein in synaptic transmission and dopaminergic neuron physiology. These latest advances add to our understanding of PD etiology and provide a central link between the genetic findings and neurodegeneration observed in sporadic PD.

DOI

10.1016/j.tins.2010.09.004

Type

Journal article

Journal

Trends Neurosci

Publication Date

12/2010

Volume

33

Pages

559 - 568

Keywords

Alternative Splicing, Animals, Dopamine, Humans, MicroRNAs, Neurons, Parkinson Disease, Synaptic Vesicles, alpha-Synuclein

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