GABA(A) receptors in aging and Alzheimer's disease.
In this article we present a comprehensive review of relevant research and reports on the GABA(A) receptor in the aged and Alzheimer's disease (AD) brain. In comparison to glutamatergic and cholinergic systems, the GABAergic system is relatively spared in AD, but the precise mechanisms underlying differential vulnerability are not well understood. Using several methods, investigations demonstrate that despite resistance of the GABAergic system to neurodegeneration, particular subunits of the GABA(A) receptor are altered with age and AD, which can induce compensatory increases in GABA(A) receptor subunits within surrounding cells. We conclude that although aging- and disease-related changes in GABA(A) receptor subunits may be modest, the mechanisms that compensate for these changes may alter the pharmacokinetic and physiological properties of the receptor. It is therefore crucial to understand the subunit composition of individual GABA(A) receptors in the diseased brain when developing therapeutics that act at these receptors.
Rissman
Robert A
RA
Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, California, USA. rrissman@salk.edu
De Blas
Angel L
AL
Armstrong
David M
DM
D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D006801:Humans; D021122:Protein Subunits / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000502:physiology
D021122:Protein Subunits; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid