IMPLICATIONS OF AGING-RELATED AND DEGENERATION-RELATED CHANGES IN ANION-EXCHANGE PROTEINS FOR THE MAINTENANCE OF NEURONAL HOMEOSTASIS

Fourier-transform infrared spectroscopy was applied to examine the nat ure and extent of changes in membrane composition and structure during the aging process of the human erythrocyte. Analysis of the Amide I r egion (1700-1600 cm(-1)) indicates an aging-related decrease in alpha- helical structure with a concomitant increase in beta-structure. These changes can be explained by structural changes in the erythrocyte ani on exchanger (band 3 or AE1) molecules, that may be caused by fragment ation, but not by aggregation. Immunohistochemical analysis of human b rain tissue shows an increase in neuronal AE protein expression with a ge and suggests an additional increase in Alzheimer's disease. Biochem ical analyses indicate that the latter may be caused by conformational changes in the AE membrane domain that are similar to those observed in AE1 during erythrocyte aging. AE proteins provide a binding site fo r the cytoskeleton in neurons, and AE-catalyzed chloride/bicarbonate e xchange plays a major role in maintenance of neuronal pH. Thus, change s in AE structure are likely to contribute to loss of neuron homeostas is during aging and in neurodegenerative diseases.