Parkin Gene Has Key Role in Human Nigral Dopaminergic Neurons
(HealthDay News) – Parkin may control dopamine utilization in the human midbrain by enhancing dopaminergic neurotransmission and suppressing dopamine oxidation, according to a study published online Feb. 7 in Nature Communications.
To investigate the role of mutations in the gene parkin in human nigral dopaminergic neurons, Houbo Jiang, Ph.D., from the State University of New York at Buffalo, and colleagues generated induced pluripotent stem cells from normal subjects and patients with Parkinson's disease with parkin mutations.
The researchers found that the absence of parkin in human midbrain dopaminergic neurons was associated with an increase in the transcription of monoamine oxidases and oxidative stress. In addition, loss of parkin significantly decreased dopamine uptake and increased its spontaneous release. These phenotypes were rescued by lentiviral expression of parkin, but not its Parkinson's disease-linked mutant.
"The study has discovered how mutations of parkin disrupt an essential function of human midbrain dopaminergic neurons -- the coordinated utilization of dopamine as a neurotransmitter and the control of dopamine toxicity," the authors write. "Further studies are needed to address why nigral dopaminergic neurons, in comparison with other types of dopaminergic neurons, are particularly vulnerable in Parkinson's disease and how parkin protects against these vulnerabilities."