ABCC9/SUR2 in the brain: Implications for hippocampal sclerosis of aging and a potential therapeutic target.

摘要: The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins a component ATP-sensitive potassium ("KATP") channel, metabolic sensor for stress and/or hypoxia that has been shown to change aging. KATP channel also helps regulate neurovascular unit. Most brain cell types express neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, endothelial cells. Thus it is not surprising variants associated with risk diseases. For example, Cantu syndrome result mutations; we discuss manifestations this genetic syndrome. More common disorders linked include hippocampal sclerosis aging (HS-Aging), sleep disorders, depression. HS-Aging neurological disease pathologic features both neurodegenerative (aberrant TDP-43) cerebrovascular (arteriolosclerosis) disease. As potential therapeutic intervention, pharmacopeia agonists antagonists, so ABCC9/SUR2 may provide "druggable target", relevant perhaps Alzheimer's We conclude more work required better understand roles during health conditions.