Department of Neurosciences, Center for Neural Circuits and Behavior, UCSD, La Jolla 92093, United States.
Department of Neurosciences, Center for Neural Circuits and Behavior, UCSD, La Jolla 92093, United States.
Semin Cell Dev Biol. 2023 Apr;139:84-92. doi: 10.1016/j.semcdb.2022.03.032. Epub 2022 Mar 31.
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.
相当一部分患有阿尔茨海默病病理的大脑是从认知正常的患者中获得的，这表明这些个体大脑中的差异使他们对这种疾病具有抵抗力。在这里，我们描述了最近的一些方法，这些方法专门提高了突触的弹性，因为突触的丧失被认为是阿尔茨海默病患者大脑中的第一个变化。我们首先讨论了增加神经营养因子和保护基因表达的益处的研究。接下来描述了通过作用于肌动蛋白网络蛋白、支架蛋白和抑制磷酸酶来使树突棘更强壮的有效方法。重要的是，本综述中提出的治疗策略不是通过靶向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。
