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The enhancement of amyloid precursor protein and β-site amyloid cleavage enzyme 1 interaction: Amyloid-β production with aging

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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-β (Aβ) components. However, little direct evidence has shown aging in association with Aβ. Here we show that the protein-protein interaction of amyloid precursor protein (APP) and β -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 Aβ 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 Aβ production, suggesting that endocytosis contributes to AD progression.
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Document Type: Research Article

Affiliations: Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, P.R. China., Email: [email protected]

Publication date: January 1, 2010

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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