Department of Internal Medicine, Medical College, Najran University, Najran, Saudi Arabia.
Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
J Cell Mol Med. 2024 May;28(10):e18368. doi: 10.1111/jcmm.18368.
Parkinson's disease (PD) is a neurodegenerative disorder of the brain and is manifested by motor and non-motor symptoms because of degenerative changes in dopaminergic neurons of the substantia nigra. PD neuropathology is associated with mitochondrial dysfunction, oxidative damage and apoptosis. Thus, the modulation of mitochondrial dysfunction, oxidative damage and apoptosis by growth factors could be a novel boulevard in the management of PD. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase type B (TrkB) are chiefly involved in PD neuropathology. BDNF promotes the survival of dopaminergic neurons in the substantia nigra and enhances the functional activity of striatal neurons. Deficiency of the TrkB receptor triggers degeneration of dopaminergic neurons and accumulation of α-Syn in the substantia nigra. As well, BDNF/TrkB signalling is reduced in the early phase of PD neuropathology. Targeting of BDNF/TrkB signalling by specific activators may attenuate PD neuropathology. Thus, this review aimed to discuss the potential role of BDNF/TrkB activators against PD. In conclusion, BDNF/TrkB signalling is decreased in PD and linked with disease severity and long-term complications. Activation of BDNF/TrkB by specific activators may attenuate PD neuropathology.
帕金森病（PD）是一种大脑的神经退行性疾病，由于黑质多巴胺能神经元的退行性变化，表现为运动和非运动症状。PD 的神经病理学与线粒体功能障碍、氧化损伤和细胞凋亡有关。因此，生长因子对线粒体功能障碍、氧化损伤和细胞凋亡的调节可能是 PD 治疗的一个新途径。脑源性神经营养因子（BDNF）及其受体原肌球蛋白受体激酶 B（TrkB）主要参与 PD 的神经病理学。BDNF 促进黑质多巴胺能神经元的存活，并增强纹状体神经元的功能活性。TrkB 受体的缺失会触发多巴胺能神经元的退化和α-突触核蛋白在黑质中的积累。此外，BDNF/TrkB 信号在 PD 神经病理学的早期阶段就减少了。通过特定的激活剂靶向 BDNF/TrkB 信号可能会减轻 PD 神经病理学。因此，本综述旨在讨论 BDNF/TrkB 激活剂对抗 PD 的潜在作用。总之，BDNF/TrkB 信号在 PD 中减少，并与疾病严重程度和长期并发症有关。通过特定的激活剂激活 BDNF/TrkB 可能会减轻 PD 神经病理学。
