TY - JOUR
T1 - ABCC9/SUR2 in the brain
T2 - Implications for hippocampal sclerosis of aging and a potential therapeutic target
AU - Nelson, Peter T.
AU - Jicha, Gregory A.
AU - Wang, Wang Xia
AU - Ighodaro, Eseosa
AU - Artiushin, Sergey
AU - Nichols, Colin G.
AU - Fardo, David W.
N1 - Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium ("KATP") channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The KATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is a result of ABCC9 mutations; we discuss neurologic manifestations of this genetic syndrome. More common brain disorders linked to ABCC9 gene variants include hippocampal sclerosis of aging (HS-Aging), sleep disorders, and depression. HS-Aging is a prevalent neurological disease with pathologic features of both neurodegenerative (aberrant TDP-43) and cerebrovascular (arteriolosclerosis) disease. As to potential therapeutic intervention, the human pharmacopeia features both SUR2 agonists and antagonists, so ABCC9/SUR2 may provide a "druggable target", relevant perhaps to both HS-Aging and Alzheimer's disease. We conclude that more work is required to better understand the roles of ABCC9/SUR2 in the human brain during health and disease conditions.
AB - The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium ("KATP") channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The KATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is a result of ABCC9 mutations; we discuss neurologic manifestations of this genetic syndrome. More common brain disorders linked to ABCC9 gene variants include hippocampal sclerosis of aging (HS-Aging), sleep disorders, and depression. HS-Aging is a prevalent neurological disease with pathologic features of both neurodegenerative (aberrant TDP-43) and cerebrovascular (arteriolosclerosis) disease. As to potential therapeutic intervention, the human pharmacopeia features both SUR2 agonists and antagonists, so ABCC9/SUR2 may provide a "druggable target", relevant perhaps to both HS-Aging and Alzheimer's disease. We conclude that more work is required to better understand the roles of ABCC9/SUR2 in the human brain during health and disease conditions.
KW - ABCC8
KW - Arteriolosclerosis
KW - GWAS
KW - Hippocampus
KW - Neuropathology
KW - Oldest-old
KW - SUR1
KW - SUR2A
KW - SUR2Ab
KW - SUR2B
UR - http://www.scopus.com/inward/record.url?scp=84961060846&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84961060846&partnerID=8YFLogxK
U2 - 10.1016/j.arr.2015.07.007
DO - 10.1016/j.arr.2015.07.007
M3 - Review article
C2 - 26226329
AN - SCOPUS:84961060846
SN - 1568-1637
VL - 24
SP - 111
EP - 125
JO - Ageing Research Reviews
JF - Ageing Research Reviews
ER -