Differential involvement of small G proteins in Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive deterioration of cognitive function and memory in association with the wide-spread presence of senile plaques, neurofibrillary tangles and neuronal cell death. However, its pathophysiology remains unknown. GTP-binding proteins with molecular weights of approximately 20,000 are designated small G proteins. In the present study we quantitatively analyzed the small G proteins, Ras, Rap, Ral and Rab in brains removed at autopsy from controls and AD patients to examine whether small G proteins are equally or differentially affected in AD. Western blot analysis indicated that the protein level of Ras and RalB in both the cytosolic and membranous fractions and that of Rap2 in the cytosolic fraction was significantly decreased, while that of Rab8 in the membranous fraction was significantly increased in AD brains compared with controls. The protein level of other small G proteins was not different between control and AD brains. These results suggest a differential involvement of small G proteins in AD.
Shimohama
S
S
Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyoku, Kyoto 606-8507, Japan.
Kamiya
S
S
Taniguchi
T
T
Sumida
Y
Y
Fujimoto
S
S
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D029867:Xenopus Proteins; D020691:rab GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D020725:ral GTP-Binding Proteins; D020668:rap GTP-Binding Proteins; D018631:ras Proteins / Q000378:metabolism
C119391:RalB protein, Xenopus; D029867:Xenopus Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C492198:RALA protein, human; C082377:RAB8A protein, human; D020691:rab GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D020725:ral GTP-Binding Proteins; D020668:rap GTP-Binding Proteins; D018631:ras Proteins