Open AccessThe enhancement of amyloid precursor protein and β-site amyloid cleavage enzyme 1 interaction: Amyloid-β production with aging
Author(s) -
Lin Zou,
Rongxi Yang,
Penghui Zhang,
Yi Han Dai
Publication year - 2010
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm_00000358
Subject(s) - amyloid precursor protein , endocytosis , senile plaques , p3 peptide , endocytic cycle , amyloid (mycology) , bace1 as , biochemistry of alzheimer's disease , microbiology and biotechnology , biology , population , alzheimer's disease , chemistry , biochemistry , medicine , disease , cell , environmental health , botany
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.