Analyzing dendritic spine pathology in Alzheimer's disease: problems and opportunities.
Analyzing dendritic spine pathology in Alzheimer's disease: problems and opportunities.
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DOI：
10.1007/s00401-015-1449-5
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发表时间：
2015-07
影响因子：
12.7
通讯作者：
Herms J
中科院分区：
文献类型：
--
作者：
Dorostkar MM;Zou C;Blazquez-Llorca L;Herms J
突触衰竭是阿尔茨海默病认知能力下降和记忆功能障碍的直接原因。树突棘是神经元过程上的特殊结构，在其上发生兴奋性突触接触，树突棘的丧失与突触功能的丧失直接相关。树突棘很容易用于体外和体内实验，因此在阿尔茨海默病小鼠模型中进行了详细研究。迄今为止，已经提出了大量不同的机制来导致阿尔茨海默病的树突棘功能障碍和丧失。例如，已发现β淀粉样蛋白原纤维、可扩散寡聚体或β淀粉样蛋白的细胞内积累可通过不同的机制改变树突棘的功能和结构。此外，tau蛋白过度磷酸化和小胶质细胞激活被认为是阿尔茨海默病淀粉样变性的后果，也可能导致脊柱损失。最后，在实验动物中用于模拟该疾病并阐明其发病机制的遗传和治疗干预措施可能会导致树突棘本身的改变。然而，迄今为止，这些机制尚未转化为人类疾病的成功治疗方法。在这里，我们批判性地回顾了阿尔茨海默病中最深入研究的脊柱损失机制，以及这种复杂的神经退行性疾病的动物模型中可能存在的陷阱。
Synaptic failure is an immediate cause of cognitive decline and memory dysfunction in Alzheimer’s disease. Dendritic spines are specialized structures on neuronal processes, on which excitatory synaptic contacts take place and the loss of dendritic spines directly correlates with the loss of synaptic function. Dendritic spines are readily accessible for both in vitro and in vivo experiments and have, therefore, been studied in great detail in Alzheimer’s disease mouse models. To date, a large number of different mechanisms have been proposed to cause dendritic spine dysfunction and loss in Alzheimer’s disease. For instance, amyloid beta fibrils, diffusible oligomers or the intracellular accumulation of amyloid beta have been found to alter the function and structure of dendritic spines by distinct mechanisms. Furthermore, tau hyperphosphorylation and microglia activation, which are thought to be consequences of amyloidosis in Alzheimer’s disease, may also contribute to spine loss. Lastly, genetic and therapeutic interventions employed to model the disease and elucidate its pathogenetic mechanisms in experimental animals may cause alterations of dendritic spines on their own. However, to date none of these mechanisms have been translated into successful therapeutic approaches for the human disease. Here, we critically review the most intensely studied mechanisms of spine loss in Alzheimer’s disease as well as the possible pitfalls inherent in the animal models of such a complex neurodegenerative disorder.
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影响因子：
2.5
作者：
Belichenko, PV;Masliah, E;Mobley, WC
通讯作者：
Mobley, WC
影响因子：
16.2
作者：
Bhaskar, Kiran;Konerth, Megan;Kokiko-Cochran, Olga N.;Cardona, Astrid;Ransohoff, Richard M.;Lamb, Bruce T.
通讯作者：
Lamb, Bruce T.
DOI：
10.1073/pnas.1206171109
发表时间：
2012-05-29
影响因子：
11.1
作者：
Busche, Marc Aurel;Chen, Xiaowei;Konnerth, Arthur
通讯作者：
Konnerth, Arthur
影响因子：
5.5
作者：
Bitan, G;Fradinger, EA;Teplow, DB
通讯作者：
Teplow, DB
影响因子：
14.5
作者：
Adalbert, Robert;Nogradi, Antal;Coleman, Michael P.
通讯作者：
Coleman, Michael P.