Novel approaches to increase synaptic resilience as potential treatments for Alzheimer's disease.
Novel approaches to increase synaptic resilience as potential treatments for Alzheimer's disease.
复制标题
作为对阿尔茨海默氏病潜在治疗的潜在治疗方法，采用新的方法来增加突触弹性。
DOI：
10.1016/j.semcdb.2022.03.032
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发表时间：
2023-04
影响因子：
7.3
通讯作者：
Dore, Kim
中科院分区：
文献类型：
--
作者：
Pham, Andrew Q.;Dore, Kim
关键词：
阿尔茨海默病患者的大脑中有很大一部分是从认知正常的患者那里获得的，这表明这些人大脑内部的差异使他们对疾病具有弹性。在这里，我们描述了最近专门提高突触韧性的方法，因为突触的丢失被认为是阿尔茨海默氏症患者大脑的第一个变化。我们首先讨论的研究表明，神经营养因子和保护性基因的表达增加是有益的。下面将介绍有效增强树突棘的方法，特别是通过肌动蛋白网络蛋白、支架蛋白和抑制磷酸酶发挥作用。重要的是，这篇综述中提出的治疗策略并不是通过针对斑块和缠结来治疗阿尔茨海默病，而是通过使突触对与阿尔茨海默病相关的病理具有弹性，这具有巨大的潜力。
A significant proportion of brains with Alzheimer’s disease pathology are obtained from patients that were cognitively normal, suggesting that differences within the brains of these individuals made them resilient to the disease. Here, we describe recent approaches that specifically increase synaptic resilience, as loss of synapses is considered to be the first change in the brains of Alzheimer’s patients. We start by discussing studies showing benefit from increased expression of neurotrophic factors and protective genes. Methods that effectively make dendritic spines stronger, specifically by acting through actin network proteins, scaffolding proteins and inhibition of phosphatases are described next. Importantly, the therapeutic strategies presented in this review tackle Alzheimer’s disease not by targeting plaques and tangles, but instead by making synapses resilient to the pathology associated with Alzheimer’s disease, which has tremendous potential.
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