Synaptic dysfunction and disruption of the postsynaptic drebrin-actin complex: the study of neurological disorders accompanied by cognitive deficits
Synaptic dysfunction and disruption of the postsynaptic drebrin-actin complex: the study of neurological disorders accompanied by cognitive deficits
复制标题
DOI：
--
复制
发表时间：
2007
影响因子：
4.7
通讯作者：
N. Kojima;T. Shirao
中科院分区：
文献类型：
--
作者：
N. Kojima;T. Shirao
摘要许多伴有认知缺陷的神经系统疾病，包括阿尔茨海默病（AD）和唐氏综合征，都表现出异常的树突棘形态。基于肌动蛋白的细胞骨架网络动力学对于调节棘的形态和功能至关重要。AD动物模型的最新实验数据显示，与淀粉样蛋白β（A β）积累相关的细胞内信号级联的缺陷导致突触后肌动蛋白调节机制（包括cofilin和dreplatin）的破坏。树突棘中的一种主要的F-肌动蛋白结合蛋白-突触后树突的数量与认知障碍的严重程度密切相关。我们认为，肌动蛋白调节机制的不平衡调节（dreplatin的丢失和相关的去磷酸化cofilin的增加）导致突触功能障碍，这是神经系统疾病和正常衰老的认知障碍的基础。
Manuscript 2 Abstract Many neurological disorders accompanied by cognitive deficits, including Alzheimer's disease (AD) and Down syndrome, exhibit abnormal dendritic spine morphology. Actin-based cytoskeletal network dynamics are critical for regulation of spine morphology and function. Recent experimental data from an AD animal model reveal that defects in intracellular signaling cascades related to accumulation of amyloid (A) cause disruption of postsynaptic actin-regulatory machinery, including cofilin and drebrin. The amount of postsynaptic drebrin, a major F-actin binding protein in dendritic spines, correlates well with the severity of cognitive impairment. We propose that imbalanced regulation of actin-regulatory machinery (loss of drebrin and associated increase in dephosphorylated cofilin) results in synaptic dysfunction underlying the cognitive impairment of neurological disorders and normal aging.