Pathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body disease.
Pathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body disease.
复制标题
DOI：
10.1016/j.bcp.2014.01.015
复制
发表时间：
2014-04-15
影响因子：
5.8
通讯作者：
Masliah, Eliezer
中科院分区：
文献类型：
--
作者：
Overk, Cassia R.;Masliah, Eliezer
过去几年，在对抗阿尔茨海默病（AD）和帕金森病（PD）方面取得了长足进展。人脑神经病理学研究以及体内和体外模型实验支持这样的观点：即使在神经退行性过程的最早阶段，突触也会受到影响。本手稿的目的是回顾 AD 和 PD 中突触损伤的一些机制。一些证据支持这样的观点：β淀粉样蛋白、α-突触核蛋白和 Tau 的寡聚神经毒性物质可能导致疾病早期阶段突触衰竭的发病机制。寡聚物导致突触损伤的机制可能涉及谷氨酸受体和支架分子的失调，导致突触小泡和线粒体的轴突运输发生改变，随后导致树突和脊柱改变、轴突营养不良，并最终导致神经元损失。然而，虽然一些研究支持低聚物的作用，但对于有毒物质的确切性质仍存在争论。鉴于对这些疾病的早期临床和临床前诊断所做的努力，了解突触变性的分子和细胞机制对于开发针对脆弱神经元突触装置的特定生物标志物和新疗法至关重要。
Considerable progress has been made in the past few years in the fight against Alzheimer’s disease (AD) and Parkinson’s disease (PD). Neuropathological studies in human brains and experimental in vivo and in vitro models support the notion that synapses are affected even at the earliest stages of the neurodegenerative process. The objective of this manuscript is to review some of the mechanisms of synaptic damage in AD and PD. Some lines of evidence support the notion that oligomeric neurotoxic species of amyloid β, α-synuclein, and Tau might contribute to the pathogenesis of synaptic failure at early stages of the diseases. The mechanisms leading to synaptic damage by oligomers might involve dysregulation of glutamate receptors and scaffold molecules that results in alterations in the axonal transport of synaptic vesicles and mitochondria that later on lead to dendritic and spine alterations, axonal dystrophy, and eventually neuronal loss. However, while some studies support a role of oligomers, there is an ongoing debate as to the exact nature of the toxic species. Given the efforts toward earlier clinical and preclinical diagnosis of these disorders, understanding the molecular and cellular mechanisms of synaptic degeneration is crucial toward developing specific biomarkers and new therapies targeting the synaptic apparatus of vulnerable neurons.
登录
查看更多内容
影响因子：
82.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
168.9
作者：
Chartier-Harlin, MC;Kachergus, J;Destée, A
通讯作者：
Destée, A
影响因子：
4.8
作者：
Danzer, Karin M.;Ruf, Wolfgang P.;McLean, Pamela J.
通讯作者：
McLean, Pamela J.
影响因子：
6.1
作者：
Almeida, CG;Tampellini, D;Gouras, GK
通讯作者：
Gouras, GK
影响因子：
3.7
作者：
Crews L;Spencer B;Desplats P;Patrick C;Paulino A;Rockenstein E;Hansen L;Adame A;Galasko D;Masliah E
通讯作者：
Masliah E