Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
Int J Mol Sci. 2020 Jan 30;21(3):908. doi: 10.3390/ijms21030908.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by Aβ-driven synaptic dysfunction in the early phases of pathogenesis. In the synaptic context, the actin cytoskeleton is a crucial element to maintain the dendritic spine architecture and to orchestrate the spine's morphology remodeling driven by synaptic activity. Indeed, spine shape and synaptic strength are strictly correlated and precisely governed during plasticity phenomena in order to convert short-term alterations of synaptic strength into long-lasting changes that are embedded in stable structural modification. These functional and structural modifications are considered the biological basis of learning and memory processes. In this review we discussed the existing evidence regarding the role of the spine actin cytoskeleton in AD synaptic failure. We revised the physiological function of the actin cytoskeleton in the spine shaping and the contribution of actin dynamics in the endocytosis mechanism. The internalization process is implicated in different aspects of AD since it controls both glutamate receptor membrane levels and amyloid generation. The detailed understanding of the mechanisms controlling the actin cytoskeleton in a unique biological context as the dendritic spine could pave the way to the development of innovative synapse-tailored therapeutic interventions and to the identification of novel biomarkers to monitor synaptic loss in AD.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是在发病的早期阶段由 Aβ 驱动的突触功能障碍。在突触环境中，肌动蛋白细胞骨架是维持树突棘结构的关键元素，并协调由突触活动驱动的棘形态重塑。事实上，在可塑性现象期间，棘的形状和突触强度严格相关且受到精确调控，以便将突触强度的短期改变转化为嵌入稳定结构修饰中的长期变化。这些功能和结构的改变被认为是学习和记忆过程的生物学基础。在这篇综述中，我们讨论了现有证据表明在 AD 突触失败中，棘状突的肌动蛋白细胞骨架的作用。我们回顾了肌动蛋白细胞骨架在棘状突形成中的生理功能以及肌动蛋白动力学在胞吞作用机制中的贡献。内化过程涉及 AD 的不同方面，因为它控制着谷氨酸受体膜水平和淀粉样蛋白的产生。在树突棘这样独特的生物学环境中，详细了解控制肌动蛋白细胞骨架的机制可能为开发创新的突触特异性治疗干预措施铺平道路，并为监测 AD 中的突触丧失确定新的生物标志物。
