Presenilin: A Multi-Functional Molecule in the Pathogenesis of Alzheimer’s Disease and Other Neurodegenerative Diseases
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Published:2024-02-01
Issue:3
Volume:25
Page:1757
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Sun Yang1,
Islam Sadequl1,
Michikawa Makoto2,
Zou Kun1
Affiliation:
1. Department of Biochemistry, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan
2. Department of Geriatric Medicine, School of Life Dentistry at Niigata, The Nippon Dental University, Niigata 951-8580, Japan
Abstract
Presenilin, a transmembrane protein primarily known for its role in Alzheimer’s disease (AD) as part of the γ-secretase complex, has garnered increased attention due to its multifaceted functions in various cellular processes. Recent investigations have unveiled a plethora of functions beyond its amyloidogenic role. This review aims to provide a comprehensive overview of presenilin’s diverse roles in AD and other neurodegenerative disorders. It includes a summary of well-known substrates of presenilin, such as its involvement in amyloid precursor protein (APP) processing and Notch signaling, along with other functions. Additionally, it highlights newly discovered functions, such as trafficking function, regulation of ferritin expression, apolipoprotein E (ApoE) secretion, the interaction of ApoE and presenilin, and the Aβ42-to-Aβ40-converting activity of ACE. This updated perspective underscores the evolving landscape of presenilin research, emphasizing its broader impact beyond established pathways. The incorporation of these novel findings accentuates the dynamic nature of presenilin’s involvement in cellular processes, further advancing our comprehension of its multifaceted roles in neurodegenerative disorders. By synthesizing evidence from a range of studies, this review sheds light on the intricate web of presenilin functions and their implications in health and disease.
Funder
Grant-in-Aid for Scientific Research
Ministry of Education, Culture, Sports, Science, and Technology, Japan
AMED
the 24th General Assembly of the Japanese Association of Medical Sciences
Daiko Foundation
Hirose International Scholarship Foundation
Hori Sciences and Arts Foundation
Daiwa Securities Foundation
Hirose Foundation
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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