一种半合成糖鞘脂（LIGA20）可降低原代神经元培养物中2,4,5-三羟基苯丙氨酸的神经毒性。

A semisynthetic glycosphingolipid (LIGA20) reduces 2,4, 5-trihydroxyphenylalanine neurotoxicity in primary neuronal cultures.

作者信息

Skaper S D, Fadda E, Facci L, Manev H

机构信息

Fidia Research Laboratories, Abano Terme, Italy.

出版信息

Eur J Pharmacol. 1993 Oct 12;243(1):91-3. doi: 10.1016/0014-2999(93)90173-f.

DOI:10.1016/0014-2999(93)90173-f

PMID:8253129

Abstract

The semisynthetic glycosphingolipid derivative II3Neu5-AcGgOse4-2-d-erythro-1,3-dihydroxy-2-chloro-acetamid e-4-trans- octadacene (LIGA20) attenuated injury induced by the excitotoxic L-dopa metabolite 2,4,5-trihydroxyphenylalanine (TOPA) in cultures of rat cerebellar granule cells when presented simultaneously with TOPA (EC50; 9 microM LIGA20). The natural glycosphingolipid ganglioside GM1 up to 200 microM was not neuroprotective as cotreatment, although pretreatment of cells for 2 h was efficacious. This greater potency and speed of LIGA20 action extended to limiting TOPA-induced death of cultured mesencephalic dopaminergic neurons. These data suggest that LIGA20 may have therapeutic potential for the treatment of disorders associated with excitotoxic processes.

摘要

半合成糖鞘脂衍生物II3Neu5 - AcGgOse4 - 2 - d - 赤藓糖型 - 1,3 - 二羟基 - 2 - 氯 - 乙酰胺基 - 4 - 反式 - 十八碳烯（LIGA20）与兴奋性毒性L - 多巴代谢物2,4,5 - 三羟基苯丙氨酸（TOPA）同时作用于大鼠小脑颗粒细胞培养物时，可减轻TOPA诱导的损伤（半数有效浓度；9 microM LIGA20）。高达200 microM的天然糖鞘脂神经节苷脂GM1作为联合治疗时没有神经保护作用，尽管细胞预处理2小时是有效的。LIGA20作用的这种更高效力和更快速度扩展到限制TOPA诱导的中脑多巴胺能神经元培养物的死亡。这些数据表明，LIGA20可能具有治疗与兴奋性毒性过程相关疾病的潜力。