Ferreira Ana Flávia F, Britto Luiz Roberto G
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Neural Regen Res. 2023 Aug;18(8):1652-1656. doi: 10.4103/1673-5374.360343.
The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating mechanism is dependent on reactive oxygen species. In pathological conditions, transient receptor potential melastatin 2 is overactivated, leading to a Ca influx that alters cell homeostasis and promotes cell death. The role of transient receptor potential melastatin 2 in neurodegenerative diseases, including Alzheimer's disease and ischemia, has already been described and reviewed. However, data on transient receptor potential melastatin 2 involvement in Parkinson's disease pathology has emerged only in recent years and the issue lacks review studies that focus specifically on this topic. The present review aims to elucidate the role of the transient receptor potential melastatin 2 channel in Parkinson's disease by reviewing, summarizing, and discussing the in vitro, in vivo, and human studies published until August 2022. Here we describe fourteen studies that evaluated the transient receptor potential melastatin 2 channel in Parkinson's disease. The Parkinson's disease model used, transient receptor potential melastatin 2 antagonist and genetic approaches, and the main outcomes reported were discussed. The studies described transient receptor potential melastatin 2 activation and enhanced expression in different Parkinson's disease models. They also evidenced protective and restorative effects when using transient receptor potential melastatin 2 antagonists, knockout, or silencing. This review provides a literature overview and suggests where there is a need for more research. As a perspective point, this review shows evidence that supports transient receptor potential melastatin 2 as a pharmacological target for Parkinson's disease in the future.
瞬时受体电位香草酸亚型2是瞬时受体电位（TRP）家族中一种可通透钙的阳离子通道成员。瞬时受体电位香草酸亚型2也被称为氧化应激激活通道，其门控机制依赖于活性氧。在病理条件下，瞬时受体电位香草酸亚型2过度激活，导致钙离子内流，从而改变细胞内稳态并促进细胞死亡。瞬时受体电位香草酸亚型2在包括阿尔茨海默病和局部缺血在内的神经退行性疾病中的作用已有描述和综述。然而，关于瞬时受体电位香草酸亚型2参与帕金森病病理过程的数据直到近年来才出现，且该问题缺乏专门针对此主题的综述研究。本综述旨在通过回顾、总结和讨论截至2022年8月发表的体外、体内和人体研究，阐明瞬时受体电位香草酸亚型2通道在帕金森病中的作用。在此，我们描述了14项评估帕金森病中瞬时受体电位香草酸亚型2通道的研究。讨论了所使用的帕金森病模型、瞬时受体电位香草酸亚型2拮抗剂和基因方法，以及所报告的主要结果。这些研究描述了瞬时受体电位香草酸亚型2在不同帕金森病模型中的激活和表达增强。它们还证明了使用瞬时受体电位香草酸亚型2拮抗剂、基因敲除或基因沉默时的保护和恢复作用。本综述提供了文献概述，并指出了需要更多研究的方向。从一个角度来看，本综述显示了支持瞬时受体电位香草酸亚型2在未来作为帕金森病药理学靶点的证据。
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