Guo Ji-Feng, He Shuang, Kang Ji-Feng, Xu Qian, Hu Ya-Cen, Zhang Hai-Nan, Wang Chun-Yu, Yan Xin-Xiang, Tang Bei-Sha
Department of Neurology, Xiangya Hospital, Central South UniversityChangsha 410008, Hunan, People's Republic of China; State Key Laboratory of Medical GeneticsChangsha 410008, Hunan, People's Republic of China; Key Laboratory of Human Province In Neurodegenerative Disorders, Central South UniversityChangsha 410008, Hunan, People's Republic of China; Neurodegenerative Disorders Research Center, Central South UniversityChangsha 410008, Hunan, People's Republic of China.
Department of Neurology, Xiangya Hospital, Central South University Changsha 410008, Hunan, People's Republic of China.
Int J Clin Exp Med. 2015 Oct 15;8(10):18158-64. eCollection 2015.
Rasagiline, a novel monoamine oxidase (MAO)-B inhibitor, has a mild to moderate effect in relieving Parkinson's disease (PD) symptoms as well as unique neuroprotective effects. Previous studies demonstrated rasagiline protect neurons by regulating Bcl-2 family proteins. Our study aimed to study whether Bcl-2-associated athanogene (BAG)-family proteins, which were reported closely associated with neurodegenerative disease, were involved in the neuroprotective effect of rasagiline. We found that after the administration of 1-methy1-4-phenvl-1,2,3,6-tetrahvdropvridine (MPTP), BAG2 and BAG5 proteins were up-regulated in the substantia nigra dopaminergic neurons of PD mouse model. A further increase of BAG2 and BAG5 was detected after intragastric administration of rasagiline to post-MPTP lesioned mice. Thus, the current study proved the association of BAG family proteins with PD, and suggested the involvement and a positive role of BAG2, BAG5 in the neuroprotection of rasagiline. These preliminary results implicate a novel pathway for further study on neuroprotection of rasagiline.
雷沙吉兰是一种新型单胺氧化酶(MAO)-B抑制剂,在缓解帕金森病(PD)症状方面具有轻度至中度疗效,还具有独特的神经保护作用。先前的研究表明,雷沙吉兰可通过调节Bcl-2家族蛋白来保护神经元。我们的研究旨在探讨与神经退行性疾病密切相关的Bcl-2相关抗凋亡基因(BAG)家族蛋白是否参与雷沙吉兰的神经保护作用。我们发现,在给予1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)后,PD小鼠模型黑质多巴胺能神经元中的BAG2和BAG5蛋白上调。在对MPTP损伤后的小鼠灌胃给予雷沙吉兰后,检测到BAG2和BAG5进一步增加。因此,本研究证实了BAG家族蛋白与PD的关联,并提示BAG2、BAG5参与雷沙吉兰的神经保护作用并发挥积极作用。这些初步结果为进一步研究雷沙吉兰的神经保护作用暗示了一条新途径。