Involvement of neuronal anion exchange proteins in cell death in Alzheimer's disease.
Anion exchange (AE) proteins are present in human neurons in the brain. Immunohistochemical data indicate that their apparent expression level increases with age, and especially with degeneration in Alzheimer's disease-affected brain areas. The increase in immunoreactivity is probably caused by changes in AE structure that lead to an increased accessibility of hitherto hidden epitopes. These epitopes correspond to regions in the membrane domain that are involved in generation of senescent cell-specific antigen from AE1 in aging erythrocytes. Elucidation of the molecular nature of these changes and the underlying mechanisms, will lead to insight in the processes that govern aging- and degeneration-associated perturbation of membrane integrity. AE-mediated chloride/bicarbonate exchange is a major component in the regulation of intracellular pH. The functional consequences of changes in AE structure may range from acidosis, disturbance of cytoskeleton integrity, and untimely or impaired recognition of cells by components of the immune system, such as microglia. A molecular and physiological description of these changes will establish AE proteins as valuable tools in elucidating the processes of normal aging, and the disturbances in aging-related diseases such as Alzheimer's disease.
Bosman
G J
GJ
Department of Biochemistry, Faculty of Medicine, University of Nijmegen, The Netherlands.
Renkawek
K
K
Van Workum
F P
FP
Bartholomeus
I G
IG
De Grip
W J
WJ
D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D017487:Ankyrins / Q000032:analysis / Q000276:immunology; D000918:Antibody Specificity; D017920:Antiporters / Q000032:analysis / Q000502:physiology*; D001253:Astrocytes / Q000737:chemistry; D001639:Bicarbonates / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology; D009447:Neuroblastoma; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000502:physiology
D017487:Ankyrins; D017920:Antiporters; D001639:Bicarbonates; D002712:Chlorides; D008565:Membrane Proteins