α-Synuclein and dopamine at the crossroads of Parkinson's disease.
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.
Department of Physiology, Anatomy and Genetics; Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Lara Lourenço
LL
Venda
Stephanie J
SJ
Cragg
Vladimir L
VL
Buchman
Richard
R
Wade-Martins
D017398:Alternative Splicing; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013572:Synaptic Vesicles / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs; D051844:alpha-Synuclein; D004298:Dopamine