Muscarinic Acetylcholine Receptor M5 (CHRM5) Antibody

Background

CHRM5 encodes the muscarinic acetylcholine receptor M5, the least abundant subtype of the muscarinic receptor family. Unlike CHRM4, CHRM5 primarily couples to Gq/11 proteins, activating phospholipase C (PLC) and increasing the production of inositol triphosphate (IP3) and diacylglycerol (DAG). This cascade results in an elevation of intracellular calcium ion levels and downstream activation of protein kinase C (PKC). CHRM5 is expressed in limited regions of the central nervous system, including the midbrain dopamine neurons, hippocampus, and vascular endothelial cells. Its activation plays a key role in cerebral blood flow regulation, dopamine release, and synaptic plasticity, which are critical for processes such as learning, memory formation, and reward processing. CHRM5 is also implicated in addiction and substance abuse disorders, as its activation enhances dopamine release in the brain's reward centers. CHRM5-selective agonists are of therapeutic interest for improving cognitive function in diseases like Alzheimer's disease and vascular dementia, while antagonists could be useful for modulating excessive cholinergic activity. Additionally, CHRM5 is explored for its role in promoting vasodilation of cerebral arteries, which may have implications in treating stroke or ischemic conditions. Genetic variants of CHRM5 are associated with susceptibility to neurodegenerative diseases, emphasizing its role as a critical therapeutic target in neurology and psychiatry.