The enhancement of amyloid precursor protein and beta-site amyloid cleavage enzyme 1 interaction: amyloid-beta production with aging.
Aging is considered a high risk factor for Alzheimer's disease (AD), which is one of the most prevalent neurodegenerative disorders in the elderly population. The major pathologic feature of AD is senile plaques mainly containing amyloid-beta (Abeta) components. However, little direct evidence has shown aging in association with Abeta. Here we show that the protein-protein interaction of amyloid precursor protein (APP) and beta -site amyloid cleavage enzyme 1 (BACE1) is enhanced by the fluorescence resonance energy transfer (FRET) assay during the aging process, and the APP-BACE1 complex accumulates in the endosome in the IMR-90 fibroblast (NHF) cellular aging models. Moreover, enhanced Abeta is observed in aged cells, rat brain homogenates and human serum. Interestingly, addition of the dominant-negative mutant of Rab5, a small G-protein Rab5 involved in the endocytic process, inhibits the aging-related APP-BACE1 interaction and Abeta production, suggesting that endocytosis contributes to AD progression.
Zou
Lin
L
Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, P.R. China. zoulin_74@yahoo.com.cn
Yang
Rongxi
R
Zhang
Penghui
P
Dai
Yi
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008875:Middle Aged; D051381:Rats; D055815:Young Adult; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D020696:rab5 GTP-Binding Proteins