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Updated: Aug 15, 2026

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
The neuronal death protein par-4 mediates dopaminergic synaptic plasticity
Mark P Mattson1, Marc Gleichmann
1Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA. mattsonm@grc.nia.nih.gov
Abstract:
Par-4, discovered in a screen for genes whose expression is increased in prostate tumor cells undergoing apoptosis, participates in physiological and pathological nerve cell death. A new study, however, provides evidence for an unexpected role for Par-4 in regulating synaptic transmission in the brain: Par-4 binds to the D2 dopamine receptor (D2DR) and modulates its activity. Mice in which the function of Par-4 is disrupted exhibit impaired dopaminergic neurotransmission, resulting in a depression-like syndrome. Several other cell death-related proteins also appear to function in regulating synaptic plasticity, suggesting that a better understanding of the functions of these proteins may lead to novel therapeutic approaches for a psychiatric and neurodegenerative disorders.
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