Recent advances in the understanding of the role of synaptic proteins in Alzheimer's Disease and other neurodegenerative disorders
Recent advances in the understanding of the role of synaptic proteins in Alzheimer's Disease and other neurodegenerative disorders
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DOI：
10.3233/jad-2001-3117
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发表时间：
2001-01-01
影响因子：
4
通讯作者：
Masliah, Eliezer
中科院分区：
文献类型：
--
作者：
Masliah, Eliezer
突触损伤是许多神经退行性疾病如阿尔茨海默病（AD）常见的早期病理事件，并且与认知障碍最相关。AD和其他神经退行性疾病中涉及的几种分子在突触功能中起重要作用，并且当错误折叠时聚集并形成淀粉样纤维。具有淀粉样蛋白结构域的突触蛋白包括淀粉样蛋白/β-蛋白前体、朊病毒蛋白、亨廷顿蛋白、共济失调蛋白-1和α-突触核蛋白。突触蛋白的改变导致突触损伤的两种可能机制是：1）错误折叠或聚集的突触分子失去了它们的正常功能和/或2）它们获得了毒性能力。最近的研究支持这样一种可能性，即低聚物是有毒的，而聚合物可能是无活性的。寡聚体触发突触丢失的机制可能与它们一旦进入细胞核和/或在内质网积聚就触发应激信号的能力有关。
Synaptic damage is an early pathological event common to many neurodegenerative disorders such as Alzheimer's disease (AD) and is the best correlate to the cognitive impairment. Several molecules involved in AD and in other neurodegenerative disorders play an important role in synaptic function and when misfolded aggregate and form amyloid fibrils. Synaptic proteins with an amyloid domain include amyloid / 3-protein precursor, prion protein, huntingtin, ataxin-1 and a-synuclein. Two of the possible mechanisms by which alterations in synaptic proteins lead to synapse damage are: 1) misfolded or aggregated synaptic molecules have lost their normal function and/or 2) they have gained a toxic capacity. Recent studies support the possibility that while oligomers are toxic, polymers might be inactive. The mechanisms by which oligomers trigger synapse loss could be related to their ability to triggers stress signals once they enter the nucleus and/or accumulate at the endoplasmic reticulum.