GPR68 Is a Neuroprotective Proton Receptor in Brain Ischemia.

Area of Science:

• Neuroscience
• Molecular Biology
• Pathophysiology

Background:

• Brain acidosis is common in neurological conditions such as stroke.
• Acidosis presents complex effects, causing both harm and protection to brain tissue.

Purpose of the Study:

• To investigate the existence of a specific proton receptor in neurons.
• To determine if this receptor can counteract injury caused by brain acidosis.

Main Methods:

• Analysis of proton-sensitive G protein-coupled receptors (GPCRs) expression in the brain.
• In vitro examination of acidosis-induced signaling pathways.
• In vitro and in vivo studies of neuronal injury in mouse models.

Main Results:

• GPR68, a proton-sensitive GPCR, is expressed in both mouse and human brains.
• GPR68 activation provided neuroprotection under acidotic and ischemic conditions.
• GPR68 mediated acidosis-induced protein kinase C (PKC) activation, and its inhibition worsened injury.

Conclusions:

• Neuronal acid signaling involves a neuroprotective metabotropic pathway.
• GPR68 represents a potential therapeutic target for mitigating neuronal damage in ischemia and other neurological diseases.