Glycogen synthase kinase 3beta inhibitor Chir025 reduces neuronal death resulting from oxygen-glucose deprivation, glutamate excitotoxicity, and cerebral ischemia
Abstract
The serine/threonine kinase, glycogen synthase kinase 3beta (GSK3beta), is abundant in CNS and is neuron specific. GSK3beta plays a pivotal role in the regulation of numerous cellular functions. GSK3beta phosphorylates and thereby regulates many metabolic, signaling, and structural proteins which can influence cell survival. Increased GSK3beta correlates with increased cell death, whereas reduced GSK3beta expression correlates with increased cell survival. We report that the GSK3beta inhibitor Chir025 is neuroprotective in vitro and in vivo. First, Chir025 reduced cultured hippocampal neuron death following glutamate exposure by 15-20% versus vehicle-treated controls. Second, Chir025 significantly reduced cultured cortical neuron death following oxygen-glucose deprivation (OGD) by approximately 50%. Third, Chir025 reduced infarct size following focal cerebral ischemia by nearly 20%. There were no significant differences in the number of TUNEL-positive neurons or in caspase-3 and -9 activities between Chir025- and vehicle-treated rats, although Chir025 elevated cytosolic Bcl-2 expression. These data show that Chir025-mediated inhibition of GSK3beta is neuroprotective and that the mechanism is probably not anti-apoptotic.
References
Overexpression of HSP72 after induction of experimental stroke protects neurons from ischemic damage
Citations
General versus specific actions of mild-moderate hypothermia in attenuating cerebral ischemic damage
GSK3β Inhibition Restores Impaired Neurogenesis in Preterm Neonates With Intraventricular Hemorrhage
Related Concepts
Related Feeds
BCL-2 Family Proteins
BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.
AKT Pathway
This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.
Apoptotic Caspases
Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.
Basal Ganglia
Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis
Aneurysm
Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.
Brain Ischemia
Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.