Gary W. Miller, Ph.D.
R01ES023839, P30ES019776, K99ES024570
NIEHS grantees discovered that the synaptic vesicle glycoprotein 2C (SV2C), a protein that helps regulate the release of neurotransmitters in the brain, might play a role in Parkinson’s disease (PD). The study findings suggested that SVC2 disruption is a feature of PD, and that SVC2 may be important for release of the neurotransmitter dopamine.
The researchers bred mice lacking SVC2 and found that these mice showed reduced dopamine levels in the brain and displayed decreases in motor activity. Previous studies linked dopamine disruption to PD, progressive cell loss, and increased vulnerability to toxicants.
The deletion of SVC2 in mice was also associated with a reduced response to nicotine, a chemical in cigarette smoke that was previously linked to a reduced risk of PD. Because they linked SVC2 disruption to both nicotine response and dopamine release, the authors suggested that the SV2C gene might be a factor for this previously identified association between nicotine use and reduced risk of PD.
The researchers also looked at the potential involvement of SV2C by examining postmortem human brain tissue. Compared with patients without a neurological disease, levels of SVC2 were dramatically reduced in brain tissue from patients with PD, but this was not the case for patients with Alzheimer’s disease or other neurological diseases.
Citation: Dunn AR, Stout KA, Ozawa M, Lohr KM, Hoffman CA, Bernstein AI, Li Y, Wang M, Sgobio C, Sastry N, Cai H, Caudle WM, Miller GW. 2017. Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease. Proc Natl Acad Sci U S A 114(11):E2253-E2262.