Current experimental disease-modifying therapeutics for multiple system atrophy.
Current experimental disease-modifying therapeutics for multiple system atrophy.
复制标题
DOI：
10.1007/s00702-021-02406-z
复制
发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Stefanova N
中科院分区：
文献类型：
--
作者：
Lemos M;Wenning GK;Stefanova N
多系统萎缩(MSA)是一种具有挑战性的神经退行性疾病，早期诊断困难且往往不准确，至今仍缺乏有效的治疗方法。它的特点是临床表现多变，伴有帕金森氏症、小脑性共济失调、自主神经功能障碍和锥体体征，进展迅速，临床病程积极。只有在尸检中发现独特的少突胶质细胞胞质包涵体(GCI)，主要由错误折叠和聚集的α-突触核蛋白(α-Syn)组成，才有可能做出明确的尸检诊断。α-Syn在少突胶质细胞内堆积和聚集的过程被认为是主要的病理事件之一。然而，MSA被认为是一种多因素疾病，有多种致病事件共同作用，包括神经炎症、氧化应激和神经营养支持中断等。这里讨论的治疗方法是基于我们目前对MSA发病机制的理解，以及过去20年进行的临床前和临床治疗研究的结果。我们总结了主要的治疗多发性硬化的疾病的方法，包括靶向α-Syn病理，调节神经炎症和加强神经保护。总而言之，我们概述了一些与需要克服临床前研究和临床研究之间的差距，以成功地在MSA中进行疾病修改的相关挑战。
Multiple system atrophy (MSA) is a challenging neurodegenerative disorder with a difficult and often inaccurate early diagnosis, still lacking effective treatment. It is characterized by a highly variable clinical presentation with parkinsonism, cerebellar ataxia, autonomic dysfunction, and pyramidal signs, with a rapid progression and an aggressive clinical course. The definite MSA diagnosis is only possible post-mortem, when the presence of distinctive oligodendroglial cytoplasmic inclusions (GCIs), mainly composed of misfolded and aggregated α-Synuclein (α-Syn) is demonstrated. The process of α-Syn accumulation and aggregation within oligodendrocytes is accepted one of the main pathological events underlying MSA. However, MSA is considered a multifactorial disorder with multiple pathogenic events acting together including neuroinflammation, oxidative stress, and disrupted neurotrophic support, among others. The discussed here treatment approaches are based on our current understanding of the pathogenesis of MSA and the results of preclinical and clinical therapeutic studies conducted over the last 2 decades. We summarize leading disease-modifying approaches for MSA including targeting α-Syn pathology, modulation of neuroinflammation, and enhancement of neuroprotection. In conclusion, we outline some challenges related to the need to overcome the gap in translation between preclinical and clinical studies towards a successful disease modification in MSA.
登录
查看更多内容
影响因子：
12.7
作者：
Ettle B;Kerman BE;Valera E;Gillmann C;Schlachetzki JC;Reiprich S;Büttner C;Ekici AB;Reis A;Wegner M;Bäuerle T;Riemenschneider MJ;Masliah E;Gage FH;Winkler J
通讯作者：
Winkler J
影响因子：
14.5
作者：
Cykowski, Matthew D.;Coon, Elizabeth A.;Parisi, Joseph E.
通讯作者：
Parisi, Joseph E.
华裔多系统萎缩患者COQ2基因突变扫描
影响因子：
4.2
作者：
Chen, Yong Ping;Zhao, Bi;Shang, Hui-Fang
通讯作者：
Shang, Hui-Fang
影响因子：
6.6
作者：
BECK, RO;BETTS, CD;FOWLER, CJ
通讯作者：
FOWLER, CJ
影响因子：
3.3
作者：
Diguet, E;Fernagut, PO;Tison, F
通讯作者：
Tison, F