DOI: 10.1002/ame2.12313
Cellular response to β- amyloid neurotoxicity in Alzheimer's disease and implications in new therapeutics
Haolin Zhang1
Xianghua Li1
Xiaoli Wang1
Jiayu Xu1
Felice Elefant2
Juan Wang1
1.Faculty of Environment and Life,Beijing University of Technology,Beijing,China2.Department of Biology,Drexel University,Philadelphia,Pennsylvania,USA
摘要：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 thera-peutics 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 1- 42 , N- terminally truncated, glutaminyl cyclase (QC) catalyzed, and pyroglutamate- modified Aβ (pEAβ) is also highly amyloidogenic and far more cytotoxic. The extracel-lular monomeric Aβ x- 42 (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 cel-lular 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-i nduced 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.
机标关键词：alzheimercellularamyloiddiseaseimplicationsneurotoxicityresponsetherapeutics
论文发表日期：2023-02-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 3-9 )
英文信息