Lithospermic acid attenuates 1-methyl-4-phenylpyridine-induced neurotoxicity by blocking neuronal apoptotic and neuroinflammatory pathways.
Lithospermic acid attenuates 1-methyl-4-phenylpyridine-induced neurotoxicity by blocking neuronal apoptotic and neuroinflammatory pathways.
复制标题
DOI：
10.1186/s12929-015-0146-y
复制
发表时间：
2015-05-28
影响因子：
11
通讯作者：
Shiao YJ
中科院分区：
文献类型：
--
作者：
Lin YL;Tsay HJ;Lai TH;Tzeng TT;Shiao YJ
帕金森氏症是仅次于阿尔茨海默病的第二常见的神经退行性疾病。该疾病的主要原因是黑质多巴胺能神经元的大量变性。神经细胞凋亡和神经炎症被认为是导致神经元变性的关键因素。两个导管。用1-甲基-4-苯基吡啶（MPP+）处理a细胞和ICR小鼠，诱导体外和体内神经毒性。Western blotting和免疫组化分析了小鼠体内的神经毒性、神经炎症和异常神经发生。在CATH的实验。a细胞显示，MPP+的处理损害了细胞膜的摄取，激活了caspase系统，提示MPP+的神经毒性机制可能包括坏死和凋亡。紫石籽酸的预处理可以预防这些毒性。紫石酸对caspase 3具有特异性抑制作用。在线粒体中，MPP+通过增加伴侣蛋白GRP-78的表达引起线粒体去极化和内质网应激。石精酸对上述作用均有抑制作用。在动物模型中，小鼠脑切片免疫组化显示MPP+降低多巴胺能神经元的数量，增强小胶质细胞的激活，促进黑质和海马的星形胶质细胞形成，MPP+引起海马神经发生异常。Lithospermic acid可显著减弱MPP+诱导的这些效应。紫石酸是一种潜在的候选药物，用于帕金森病的新型治疗干预。
Parkinson’s disease is the second most common neurodegenerative disorders after Alzheimer’s disease. The main cause of the disease is the massive degeneration of dopaminergic neurons in the substantia nigra. Neuronal apoptosis and neuroinflammation are thought to be the key contributors to the neuronal degeneration. Both CATH.a cells and ICR mice were treated with 1-methyl-4-phenylpyridin (MPP+) to induce neurotoxicity in vitro and in vivo. Western blotting and immunohistochemistry were also used to analyse neurotoxicity, neuroinflammation and aberrant neurogenesis in vivo. The experiment in CATH.a cells showed that the treatment of MPP+ impaired intake of cell membrane and activated caspase system, suggesting that the neurotoxic mechanisms of MPP+ might include both necrosis and apoptosis. Pretreatment of lithospermic acid might prevent these toxicities. Lithospermic acid possesses specific inhibitory effect on caspase 3. In mitochondria, MPP+ caused mitochondrial depolarization and induced endoplasmic reticulum stress via increasing expression of chaperone protein, GRP-78. All the effects mentioned above were reduced by lithospermic acid. In animal model, the immunohistochemistry of mice brain sections revealed that MPP+ decreased the amount of dopaminergic neurons, enhanced microglia activation, promoted astrogliosis in both substantia nigra and hippocampus, and MPP+ provoked the aberrant neurogenesis in hippocampus. Lithospermic acid significantly attenuates all of these effects induced by MPP+. Lithospermic acid is a potential candidate drug for the novel therapeutic intervention on Parkinson’s disease.
登录
查看更多内容
影响因子：
8.6
作者：
Bezard, Erwan;Yue, Zhenyu;Kirik, Deniz;Spillantini, Maria Grazia
通讯作者：
Spillantini, Maria Grazia
影响因子：
3.3
作者：
Kajta, M.;Rzemieniec, J.;Wojtowicz, A. K.
通讯作者：
Wojtowicz, A. K.
影响因子：
--
作者：
Brentnall M;Rodriguez-Menocal L;De Guevara RL;Cepero E;Boise LH
通讯作者：
Boise LH
影响因子：
1.8
作者：
Lin, YL;Wang, CN;Wang, WY
通讯作者：
Wang, WY
影响因子：
5.3
作者：
Fragkouli A;Doxakis E
通讯作者：
Doxakis E