Abstract
Alzheimers disease (AD) is the most common neurodegenerative disease associated with aging. One important pathologic feature of AD is the formation of extracellular senile plaques in the brain, whose major components are small peptides called β-amyloid (Aβ) that are derived from β-amyloid precursor protein (APP) through sequential cleavages by β-secretase and γ-secretase. Because of the critical role of Aβ in the pathogenesis of AD, unraveling the cellular and molecular events underlying APP/Aβ metabolism has been and remains, of paramount importance to AD research. In this article we will focus on the regulation of APP metabolism leading to Aβ generation. We will review current knowledge of the secretases (α-, β-, and γ- secretases) involved in APP processing and various molecular and cellular mechanisms underlying intracellular trafficking of APP, which is a highly regulated process and whose disturbance has direct impacts on the production of Aβ.
Keywords: Alzheimer's disease, β-amyloid, β-amyloid precursor protein, metabolism, α-secretase, β-secretase, γ-secretase, trafficking
Current Molecular Medicine
Title: Molecular and Cellular Mechanisms for Alzheimers Disease:Understanding APP Metabolism
Volume: 7 Issue: 7
Author(s): Yun-wu Zhang and Huaxi Xu
Affiliation:
Keywords: Alzheimer's disease, β-amyloid, β-amyloid precursor protein, metabolism, α-secretase, β-secretase, γ-secretase, trafficking
Abstract: Alzheimers disease (AD) is the most common neurodegenerative disease associated with aging. One important pathologic feature of AD is the formation of extracellular senile plaques in the brain, whose major components are small peptides called β-amyloid (Aβ) that are derived from β-amyloid precursor protein (APP) through sequential cleavages by β-secretase and γ-secretase. Because of the critical role of Aβ in the pathogenesis of AD, unraveling the cellular and molecular events underlying APP/Aβ metabolism has been and remains, of paramount importance to AD research. In this article we will focus on the regulation of APP metabolism leading to Aβ generation. We will review current knowledge of the secretases (α-, β-, and γ- secretases) involved in APP processing and various molecular and cellular mechanisms underlying intracellular trafficking of APP, which is a highly regulated process and whose disturbance has direct impacts on the production of Aβ.
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Cite this article as:
Zhang Yun-wu and Xu Huaxi, Molecular and Cellular Mechanisms for Alzheimers Disease:Understanding APP Metabolism, Current Molecular Medicine 2007; 7 (7) . https://dx.doi.org/10.2174/156652407782564462
DOI https://dx.doi.org/10.2174/156652407782564462 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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