The Amyloid-Beta Clearance: From Molecular Targets to Glial and Neural Cells.
The Amyloid-Beta Clearance: From Molecular Targets to Glial and Neural Cells.
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DOI：
10.3390/biom13020313
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发表时间：
2023-02-07
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
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淀粉样蛋白- β (Aβ)斑块在大脑中的沉积是阿尔茨海默病（AD）的主要病理特征之一。它可能发生在临床症状出现前20-30年。Aβ产生与清除之间的不平衡是导致AD的主要原因之一。早期增强Aβ清除是一种有吸引力的AD预防和治疗策略。几十年来，使用小分子、多肽和单克隆抗体药物直接抑制Aβ的产生和聚集在临床试验中没有取得令人满意的效果。需要新的方法来理解和对抗Aβ沉积。神经功能障碍是一个复杂的过程，它整合了大脑中不同类型细胞的功能。非神经元在阿尔茨海默病中的作用尚未完全阐明。深入了解神经元和非神经元之间的相互作用有助于阐明Aβ的形成和确定有效的药物靶点。阿尔茨海默病患者来源的多能干细胞（PSCs）包含完整的疾病背景信息，并且在体外具有分化为各种类型的神经元和非神经元的潜力，这可能为阿尔茨海默病的治疗带来新的见解。本文系统回顾了近年来有关Aβ清除的最新研究，阐明了小胶质细胞、星形胶质细胞和神经元之间的相互作用在Aβ斑块反应中的作用，这将有助于探索通过细胞分化技术利用诱导性PSCs （iPSCs）重建AD疾病模型的方法，并验证模型在理解Aβ斑块形成中的应用。本综述可能为寻找预防和延缓AD发展的线索提供最有希望的方向。
The deposition of amyloid-beta (Aβ) plaques in the brain is one of the primary pathological characteristics of Alzheimer’s disease (AD). It can take place 20–30 years before the onset of clinical symptoms. The imbalance between the production and the clearance of Aβ is one of the major causes of AD. Enhancing Aβ clearance at an early stage is an attractive preventive and therapeutic strategy of AD. Direct inhibition of Aβ production and aggregation using small molecules, peptides, and monoclonal antibody drugs has not yielded satisfactory efficacy in clinical trials for decades. Novel approaches are required to understand and combat Aβ deposition. Neurological dysfunction is a complex process that integrates the functions of different types of cells in the brain. The role of non-neurons in AD has not been fully elucidated. An in-depth understanding of the interactions between neurons and non-neurons can contribute to the elucidation of Aβ formation and the identification of effective drug targets. AD patient-derived pluripotent stem cells (PSCs) contain complete disease background information and have the potential to differentiate into various types of neurons and non-neurons in vitro, which may bring new insight into the treatment of AD. Here, we systematically review the latest studies on Aβ clearance and clarify the roles of cell interactions among microglia, astroglia and neurons in response to Aβ plaques, which will be beneficial to explore methods for reconstructing AD disease models using inducible PSCs (iPSCs) through cell differentiation techniques and validating the applications of models in understanding the formation of Aβ plaques. This review may provide the most promising directions of finding the clues for preventing and delaying the development of AD.
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影响因子：
4.7
作者：
Mohamed Asik R;Suganthy N;Aarifa MA;Kumar A;Szigeti K;Mathe D;Gulyás B;Archunan G;Padmanabhan P
通讯作者：
Padmanabhan P
影响因子：
4.8
作者：
Barak M;Fedorova V;Pospisilova V;Raska J;Vochyanova S;Sedmik J;Hribkova H;Klimova H;Vanova T;Bohaciakova D
通讯作者：
Bohaciakova D
影响因子：
5.4
作者：
Chen, Jingfei;Long, Zhimin;He, Guiqiong
通讯作者：
He, Guiqiong
影响因子：
15.1
作者：
Bemiller SM;McCray TJ;Allan K;Formica SV;Xu G;Wilson G;Kokiko-Cochran ON;Crish SD;Lasagna-Reeves CA;Ransohoff RM;Landreth GE;Lamb BT
通讯作者：
Lamb BT
影响因子：
16.6
作者：
Amin L;Harris DA
通讯作者：
Harris DA