Vaidya Bhupesh, Sharma Shyam Sunder
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, India.
Front Cell Dev Biol. 2020 Nov 20;8:584513. doi: 10.3389/fcell.2020.584513. eCollection 2020.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the symptoms of motor deficits and cognitive decline. There are a number of therapeutics available for the treatment of PD, but most of them suffer from serious side effects such as bradykinesia, dyskinesia and on-off effect. Therefore, despite the availability of these pharmacological agents, PD patients continue to have an inferior quality of life. This has warranted a need to look for alternate strategies and molecular targets. Recent evidence suggests the Transient Receptor Potential (TRP) channels could be a potential target for the management of motor and non-motor symptoms of PD. Though still in the preclinical stages, agents targeting these channels have shown immense potential in the attenuation of behavioral deficits and signaling pathways. In addition, these channels are known to be involved in the regulation of ionic homeostasis, which is disrupted in PD. Moreover, activation or inhibition of many of the TRP channels by calcium and oxidative stress has also raised the possibility of their paramount involvement in affecting the other molecular mechanisms associated with PD pathology. However, due to the paucity of information available and lack of specificity, none of these agents have gone into clinical trials for PD treatment. Considering their interaction with oxidative stress, apoptosis and excitotoxicity, TRP channels could be considered as a potential future target for the treatment of PD.
帕金森病(PD)是一种神经退行性疾病,其特征为运动功能障碍和认知衰退症状。目前有多种治疗方法可用于治疗PD,但其中大多数都存在严重的副作用,如运动迟缓、运动障碍和开关效应。因此,尽管有这些药物,但PD患者的生活质量仍然较差。这就需要寻找替代策略和分子靶点。最近的证据表明,瞬时受体电位(TRP)通道可能是治疗PD运动和非运动症状的潜在靶点。尽管仍处于临床前阶段,但靶向这些通道的药物在减轻行为缺陷和信号通路方面已显示出巨大潜力。此外,已知这些通道参与离子稳态的调节,而离子稳态在PD中会受到破坏。此外,钙和氧化应激对许多TRP通道的激活或抑制也增加了它们在影响与PD病理相关的其他分子机制中起重要作用的可能性。然而,由于可用信息匮乏且缺乏特异性,这些药物均未进入PD治疗的临床试验。考虑到它们与氧化应激、细胞凋亡和兴奋性毒性的相互作用,TRP通道可被视为未来治疗PD的潜在靶点。