title: Cocaine abuse elevates alpha-synuclein and dopamine transporter levels in the human striatum.
abstract: Direct protein interactions between the dopamine transporter and alpha-synuclein demonstrate that dopamine uptake function is modulated by alpha-synuclein. We report here that chronic cocaine abuse results in an increase in alpha-synuclein expression in the human striatum. Immunoblot analysis in the ventral putamen showed that alpha-synuclein protein was increased in striatal synaptosomes from cocaine users compared with age-matched drug-free controls. [H]-Dopamine transporter uptake was increased in parallel with 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane binding to the dopamine transporter. The increase in alpha-synuclein protein was more marked in the ventromedial sectors of the striatum than in the dorsal caudate nucleus. These results demonstrate concomitant regulation of alpha-synuclein and dopamine transporter binding and function in human striatal synaptic terminals isolated from cocaine abusers. Overexpression of alpha-synuclein may play a role in cocaine-induced plasticity and regulation of dopamine synaptic tone.
authors.affiliation: Department of Neurology, University of Miami School of Medicine, Miami, FL 33101, USA.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Qin
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Ouyang
authors.forename: John
authors.initials: J
authors.lastname: Pablo
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Mash
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D002908:Chronic Disease; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D004298:Dopamine