Amyloid peptide attenuates the proteasome activity in neuronal cells.
Previous studies have suggested a possible relationship between the ubiquitin-proteasome pathway and some pathological manifestations of Alzheimer's disease (AD). This study investigated the possibility that the Abeta peptides interact with the ubiquitin-proteasome pathway inside neuronal cells. The ubiquitin-proteasome activity decreased with age in the brains of Tg2576 mice while the Abeta(1-42) levels increased. In cultured neuronal cells, an extracellular treatment of Abeta markedly decreased the proteasome activity and extracellular treated Abeta peptides were found in the cytoplasmic compartment. These results suggest that the extracellular Abeta peptides enter the cell and inhibit the proteasome activity, which might play a role in the pathogenesis of AD.
Oh
Sangsoo
S
Neuroscience Program, Ajou University, Suwon, Republic of Korea.
Hong
Hyun Seok
HS
Hwang
Enmi
E
Sim
Hae Jin
HJ
Lee
Woojin
W
Shin
Su Jeon
SJ
Mook-Jung
Inhee
I
D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D002918:Chymotrypsin / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D015233:Models, Statistical; D009447:Neuroblastoma / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions; D013997:Time Factors; D014162:Transfection; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism
D000682:Amyloid; D010455:Peptides; D025801:Ubiquitin; D049452:Green Fluorescent Proteins; D002918:Chymotrypsin; D046988:Proteasome Endopeptidase Complex