Synaptic dysfunction in Alzheimer's disease: the effects of amyloid beta on synaptic vesicle dynamics as a novel target for therapeutic intervention.
Synaptic dysfunction in Alzheimer's disease: the effects of amyloid beta on synaptic vesicle dynamics as a novel target for therapeutic intervention.
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DOI：
10.4103/1673-5374.230276
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发表时间：
2018-04
影响因子：
6.1
通讯作者：
Alifragis P
中科院分区：
文献类型：
--
作者：
Marsh J;Alifragis P
老年痴呆症最常见的形式是阿尔茨海默病。淀粉样蛋白-β42（Aβ42）（一种小疏水肽）的进行性蓄积似乎是导致疾病进展的一个重要因素。不幸的是，开发靶向Aβ42积累的疗法的尝试尚未成功治疗或甚至减缓疾病。这种失败可能表明靶向下游效应而不是肽本身的积累可能是更有效的方法。Aβ42的蓄积似乎影响细胞生理功能的各个方面。在这篇综述中，我们提供了一个概述的证据，牵连Aβ42在突触功能障碍，重点是它如何有助于在突触囊泡动力学和神经递质释放的缺陷。我们讨论的数据提供了关于Aβ42诱导的阿尔茨海默病病理学的新见解，并更详细地了解其对与疾病早期相关的突触缺陷的贡献。虽然触发突触功能障碍的确切机制仍在研究中，但迄今为止的可用数据使我们能够提出一个模型，该模型可用作指导，以产生药物干预的新治疗靶点。
The most prevalent form of dementia in the elderly is Alzheimer's disease. A significant contributing factor to the progression of the disease appears to be the progressive accumulation of amyloid-β42 (Aβ42), a small hydrophobic peptide. Unfortunately, attempts to develop therapies targeting the accumulation of Aβ42 have not been successful to treat or even slow down the disease. It is possible that this failure is an indication that targeting downstream effects rather than the accumulation of the peptide itself might be a more effective approach. The accumulation of Aβ42 seems to affect various aspects of physiological cell functions. In this review, we provide an overview of the evidence that implicates Aβ42 in synaptic dysfunction, with a focus on how it contributes to defects in synaptic vesicle dynamics and neurotransmitter release. We discuss data that provide new insights on the Aβ42 induced pathology of Alzheimer's disease and a more detailed understanding of its contribution to the synaptic deficiencies that are associated with the early stages of the disease. Although the precise mechanisms that trigger synaptic dysfunction are still under investigation, the available data so far has enabled us to put forward a model that could be used as a guide to generate new therapeutic targets for pharmaceutical intervention.
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DOI：
10.1007/s004060050102
发表时间：
1999-12-01
影响因子：
4.7
作者：
Hartmann, T
通讯作者：
Hartmann, T
影响因子：
5.6
作者：
Chang, Pishan;Chandler, Kate E.;Walker, Matthew C.
通讯作者：
Walker, Matthew C.
丙戊酸通过细胞周期蛋白依赖性激酶 5 和糖原合酶激酶 3 信号通路减少 tau 磷酸化
影响因子：
3.8
作者：
Hu, Jiang-Ping;Xie, Jing-Wei;Wang, Zhan-You
通讯作者：
Wang, Zhan-You
影响因子：
11
作者：
Hung SY;Fu WM
通讯作者：
Fu WM
DOI：
10.1083/jcb.108.5.1863
发表时间：
1989-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Benfenati F;Bähler M;Jahn R;Greengard P
通讯作者：
Greengard P