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Journal article
Cellular response to β-amyloid neurotoxicity in Alzheimer's disease and implications in new therapeutics
Animal models and experimental medicine, v 6(1)
Feb 2023
PMID: 36872303
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
β-Amyloid (Aβ) is a specific pathological hallmark of Alzheimer's disease (AD). Because of its neurotoxicity, AD patients exhibit multiple brain dysfunctions. Disease-modifying therapy (DMT) is the central concept in the development of AD therapeutics today, and most DMT drugs that are currently in clinical trials are anti-Aβ drugs, such as aducanumab and lecanemab. Therefore, understanding Aβ's neurotoxic mechanism is crucial for Aβ-targeted drug development. Despite its total length of only a few dozen amino acids, Aβ is incredibly diverse. In addition to the well-known Aβ
, N-terminally truncated, glutaminyl cyclase (QC) catalyzed, and pyroglutamate-modified Aβ (pEAβ) is also highly amyloidogenic and far more cytotoxic. The extracellular monomeric Aβ
(x = 1-11) initiates the aggregation to form fibrils and plaques and causes many abnormal cellular responses through cell membrane receptors and receptor-coupled signal pathways. These signal cascades further influence many cellular metabolism-related processes, such as gene expression, cell cycle, and cell fate, and ultimately cause severe neural cell damage. However, endogenous cellular anti-Aβ defense processes always accompany the Aβ-induced microenvironment alterations. Aβ-cleaving endopeptidases, Aβ-degrading ubiquitin-proteasome system (UPS), and Aβ-engulfing glial cell immune responses are all essential self-defense mechanisms that we can leverage to develop new drugs. This review discusses some of the most recent advances in understanding Aβ-centric AD mechanisms and suggests prospects for promising anti-Aβ strategies.
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Details
- Title
- Cellular response to β-amyloid neurotoxicity in Alzheimer's disease and implications in new therapeutics
- Creators
- Haolin Zhang - Beijing University of TechnologyXianghua Li - Beijing University of TechnologyXiaoli Wang - Beijing University of TechnologyJiayu Xu - Beijing University of TechnologyFelice Elefant - Drexel UniversityJuan Wang - Beijing University of Technology
- Publication Details
- Animal models and experimental medicine, v 6(1)
- Publisher
- Wiley
- Number of pages
- 7
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences
- Web of Science ID
- WOS:000943897400003
- Scopus ID
- 2-s2.0-85149589726
- Other Identifier
- 991020186896604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Medicine, Research & Experimental