中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (8): 1652-1656.doi: 10.4103/1673-5374.360343

• 综述:退行性病与再生 • 上一篇    下一篇

瞬时受体电位 M 通道2:帕金森病的新治疗靶点?

  

  • 出版日期:2023-08-15 发布日期:2023-02-16

The transient receptor potential melastatin 2: a new therapeutical target for Parkinson’s disease?

Ana Flávia F. Ferreira*, Luiz Roberto G. Britto   

  1. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
  • Online:2023-08-15 Published:2023-02-16
  • Contact: Ana Flávia F. Ferreira, MSc, anaffernandesf@gmail.com.
  • Supported by:
    This work was funded by Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil - Finance Code 001, to LRB), the São Paulo Research Foundation (FAPESP, Brazil, project # 2018/07366-4), and The National Council for Scientific and Technological Development (CNPq, Brazil, project #303006/2018-8, to LRB). AFFF received a PhD fellowship from FAPESP under Grant Agreement No 2020/02109-3.

Abstract: 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 Ca2+ 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. 

Key words: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine, AG490, clotrimazole, flufenamic acid, N-(p-amylcinnamoyl) anthranilic acid, Parkinson’s disease, poly-ADPR polymerase type 1 (PARP1), rotenone, paraquat,  , transient receptor potential melastatin 2 (TRPM2)