Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab, India.
Pharmacol Res. 2020 Sep;159:105026. doi: 10.1016/j.phrs.2020.105026. Epub 2020 Jun 17.
Central nervous system (CNS) disorders like Alzheimer's disease (AD), Parkinson disease (PD), stroke, epilepsy, depression, and bipolar disorder have a high impact on both medical and social problems due to the surge in their prevalence. All of these neuronal disorders share some common etiologies including disruption of Ca homeostasis and accumulation of misfolded proteins. These misfolded proteins further disrupt the intracellular Ca homeostasis by disrupting the activity of several ion channels including transient receptor potential (TRP) channels. TRP channel families include non-selective Ca permeable channels, which act as cellular sensors activated by various physio-chemical stimuli, exogenous, and endogenous ligands responsible for maintaining the intracellular Ca homeostasis. TRP channels are abundantly expressed in the neuronal cells and disturbance in their activity leads to various neuronal diseases. Under the pathological conditions when the activity of TRP channels is perturbed, there is a disruption of the neuronal homeostasis through increased inflammatory response, generation of reactive oxygen species, and mitochondrial dysfunction. Therefore, there is a potential of pharmacological interventions targeting TRP channels in CNS disorders. This review focuses on the role of TRP channels in neurological diseases; also, we have highlighted the current insights into the pharmacological modulators targeting TRP channels.
中枢神经系统 (CNS) 疾病,如阿尔茨海默病 (AD)、帕金森病 (PD)、中风、癫痫、抑郁症和双相情感障碍,由于其患病率的上升,对医疗和社会问题都有很大的影响。所有这些神经元疾病都有一些共同的病因,包括钙稳态的破坏和错误折叠蛋白质的积累。这些错误折叠的蛋白质通过破坏包括瞬时受体电位 (TRP) 通道在内的几种离子通道的活性,进一步破坏细胞内钙稳态。TRP 通道家族包括非选择性钙渗透性通道,它们作为细胞传感器发挥作用,可被各种生理化学刺激、外源性和内源性配体激活,负责维持细胞内钙稳态。TRP 通道在神经元细胞中大量表达,其活性的干扰会导致各种神经元疾病。在 TRP 通道活性受到干扰的病理条件下,通过增加炎症反应、产生活性氧和线粒体功能障碍,破坏神经元稳态。因此,针对中枢神经系统疾病的 TRP 通道的药理学干预具有潜力。这篇综述重点介绍了 TRP 通道在神经疾病中的作用;此外,我们还强调了针对 TRP 通道的药理学调节剂的最新研究进展。