Vesicle trafficking and lipid metabolism in synucleinopathy.
Vesicle trafficking and lipid metabolism in synucleinopathy.
复制标题
突触核蛋白病的囊泡运输和脂质代谢。
DOI：
10.1007/s00401-020-02177-z
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发表时间：
2021-04
影响因子：
12.7
通讯作者：
Dettmer U
中科院分区：
文献类型：
--
作者：
Fanning S;Selkoe D;Dettmer U
神经元蛋白α-突触核蛋白(αS)在帕金森氏病和其他进行性脑疾病如路易体痴呆和多系统萎缩的发病机制中起核心作用。这些疾病统称为“突触核蛋白病”，长期以来一直被认为是纯粹的蛋白质病：以蛋白质错误折叠为主要由该蛋白质(在这种情况下：α-突触核蛋白)组成的大小聚集体为特征的疾病。然而，最近对路易小体的形态观察表明，这些病变也含有丰富的囊泡和其他膜性细胞器。此外，αS的生理和病理都与细胞内囊泡运输和脂质生物学的各个方面密切相关。αS在生理上与突触和其他小泡结合，并提出了αS在囊泡生物学调节中的几个功能。家族性帕金森病连锁αS的过量和错义突变已被证明损害囊泡运输和改变脂质稳态。另一方面，囊泡运输和脂质相关基因已成为帕金森病的危险因素，表明两者之间存在双向关系。这个问题的答案是“αS的异常积聚是否会导致囊泡转运和脂质代谢紊乱，还是αS的聚集是这种损伤的后果？”可能是“两者都有”。在这里，我们回顾了αS-脂质和αS-VESIDE贩卖相互作用的现有知识，特别关注帕金森氏病和路易体痴呆。
The neuronal protein α-synuclein (αS) is central to the pathogenesis of Parkinson’s disease and other progressive brain diseases such as Lewy body dementia and multi-system atrophy. These diseases, collectively referred to as ‘synucleinopathies’, have long been considered purely proteinopathies: diseases characterized by the misfolding of a protein into small and large aggregates mainly consisting of that protein (in this case: α-synuclein). However, recent morphological insights into Lewy bodies, the hallmark neuropathology of human synucleinopathies, suggests these lesions are also rich in vesicles and other membranous organelles. Moreover, αS physiology and pathology are both strongly associated with various aspects of intracellular vesicle trafficking and lipid biology. αS physiologically binds to synaptic and other small vesicles, and several functions of αS in regulating vesicle biology have been proposed. Familial PD-linked αS excess and missense mutations have been shown to impair vesicle trafficking and alter lipid homeostasis. On the other hand, vesicle trafficking and lipid-related genes have emerged as Parkinson’s risk factors, suggesting a bidirectional relationship. The answer to the question “Does abnormal αS accumulation cause impaired vesicle trafficking and lipid dyshomeostasis or is αS aggregation the consequence of such impairments?” may be “both”. Here, we review current knowledge of the αS-lipid and αS-veside trafficking interplay, with a special focus on Parkinson’s disease and Lewy body dementia.
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影响因子：
8.6
作者：
Appel-Cresswell, Silke;Vilarino-Guell, Carles;Farrer, Matthew J.
通讯作者：
Farrer, Matthew J.
DOI：
10.1111/j.1600-0854.2008.00853.x
发表时间：
2009-02
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Ben Gedalya T;Loeb V;Israeli E;Altschuler Y;Selkoe DJ;Sharon R
通讯作者：
Sharon R
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：
6.1
作者：
Collier, Timothy J.;Srivastava, Kinshuk R.;Paumier, Katrina L.
通讯作者：
Paumier, Katrina L.
影响因子：
9.9
作者：
Clark, L. N.;Ross, B. M.;Marder, K.
通讯作者：
Marder, K.