Chemical disaggregation of alpha-synuclein fibrils as a therapy for synucleinopathies.
Chemical disaggregation of alpha-synuclein fibrils as a therapy for synucleinopathies.
复制标题
α-突触核蛋白原纤维的化学解聚作为突触核蛋白病的治疗方法。
DOI：
10.1073/pnas.2300965120
复制
发表时间：
2023-03-14
影响因子：
11.1
通讯作者：
Schekman, Randy
中科院分区：
文献类型：
--
作者：
Wu, Shenjie;Villegas, Nancy C. Hernandez;Schekman, Randy
α -突触核蛋白形成的蛋白聚集是一系列神经退行性疾病的标志，称为突触核蛋白病（也称为路易体疾病），包括帕金森病（PD）、路易体痴呆和多系统萎缩（MSA）(1)。仅在全球范围内，PD就影响了1000多万人的生活。在突触核蛋白病中，可溶性的单体α -突触核蛋白聚集成纤维状结构。在PD患者死后脑组织中，纤维状α -突触核蛋白与其他蛋白质聚集体、脂质和受损的细胞器一起构成了不溶性包涵体路易体。α核蛋白低聚物和原纤维的存在被认为有助于突触核蛋白病发病机制中的细胞毒性(2)。像许多神经退行性疾病一样，目前对PD和其他突触核蛋白病的治疗是姑息性的，旨在控制症状，但对疾病进展的影响很小。鉴于α -突触核蛋白原纤维在突触核蛋白病的病因学中可能起的作用，它是一个明显的治疗靶点。在这一期的《Proceedings》上，Murray等人(3)报道了一类新的化合物，它们在体外和体内都具有分解α -突触核蛋白原纤维的能力。
Protein aggregate formed by alpha-synuclein is the hallmark of a series of neurodegenerative disorders known as synucleinopathies (also known as Lewy body diseases), including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA)(1). Globally PD alone affects the lives of more than 10 million people. In synucleinopathies, soluble, monomeric alpha-synuclein aggregates into fibrillar structures. The fibrillar alpha-synucleins, together with other protein aggregates, lipid, and damaged organelles constitute the insoluble inclusions, Lewy Bodies, seen in postmortem brain tissue from PD patients. The presence of both alphasynuclein oligomers and fibrils has been suggested to contribute to the cytotoxicity in the pathogenesis of synucleinopathies (2). Like many neurodegenerative diseases, the current treatment for PD and other synucleinopathies is palliative, aiming to control the symptoms with regrettably little impact on the progression of the disease. Alpha-synuclein fibrils represent an obvious therapeutic target given the possible role of these aggregates in the etiology of synucleinopathies. In this issue of the Proceedings, Murray et al.(3) report a new class of compounds with the ability to disaggregate alpha-synuclein fibrils both in vitro and in vivo.
登录
查看更多内容
影响因子：
5.7
作者：
通讯作者：
--
影响因子：
25
作者：
Fan, Xuelai;Jin, Wu Yang;Lu, Jie;Wang, Jin;Wang, Yu Tian
通讯作者：
Wang, Yu Tian
影响因子：
8
作者：
Cole, Tracy A.;Zhao, Hien;Paumier, Katrina L.
通讯作者：
Paumier, Katrina L.
DOI：
10.3233/jpd-179005
发表时间：
2017
期刊：
Journal of Parkinson's disease
影响因子：
--
作者：
Goedert M;Jakes R;Spillantini MG
通讯作者：
Spillantini MG
影响因子：
8.8
作者：
Tran HT;Chung CH;Iba M;Zhang B;Trojanowski JQ;Luk KC;Lee VM
通讯作者：
Lee VM