Neurobiological Basis of Neuronal Survival

National Institute On Drug Abuse

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Abstract

In this fiscal year we have made three major discoveries in the survival of neurons. (1) The sigma-1 receptor may play a role in the population control of neurons and glia by regulating the signaling of the transcription factor Nrf2; (2) The Zinc finger protein (Znf179) is a neuroprotective molecule and is a downstream effector of sigma-1 receptor. We found that Znf179 is upregulated when brains are under ischemic stroke. Interestingly, the reactive oxygen species resulting from brain injury can cause Znf179 to enter the nucleus to interact with a transcription factor Sp1 that in turn increases the gene expression of Znf179. Thus the Znf179 can be increased upon brain injury through an autoregulatory mechanism. Additionally, we found that the sigma-1 receptor agonist DHEAS can increase the level of Znf179 that leads to protection against ischemic brain damage.