The increase of TRPM2 channel expression induces neuronal cell death and oxidative stress

Bayir M. H.

8th International Brain Research School 22 - 28 May 2023, Isparta /Türkiye., Isparta, Turkey, 22 - 28 May 2023, vol.15, pp.13

  • Publication Type: Conference Paper / Summary Text
  • Volume: 15
  • City: Isparta
  • Country: Turkey
  • Page Numbers: pp.13
  • Van Yüzüncü Yıl University Affiliated: Yes


Calcium ion (Ca2+) concentration is low inside of cells (50-100 nM) as compared to the outside of the cells (1-3 mM). Several physiological and neuronal factors such as muscle contraction, cell proliferation, and growth are induced by the Ca2+ influx. However, the excessive Ca2+ influx induces cell death and apoptosis via the activation of calcium channels. The excessive Ca2+ influx-mediated neuronal death is induced in several diseases, including the neurodegenerative diseases. The involvements of voltage gated calcium and chemical channels on the Ca2+ influx in neuronal cells have been known for a long time. In addition to the wellknown calcium channels, the new channel superfamily namely transient receptor potential (TRP) was discovered within last decades. The TRP superfamily contains 28 members in mammalian, and their activation and inhibition mechanisms are very different from the voltage gated calcium and chemical channels. TRP melastatin 2 (TRPM2) is a subfamily member of the TRPs. The TRPM2 channel's protein structure consists of an enzyme (ADP-ribose pyrophosphatase) in the C domain (Nazıroğlu et al. 2020). When the enzyme is activated by oxidative stress and ADP-ribose, it causes a rise of excessive Ca2+ influx in the brain and neurons. The increased expression of TRPM2 channels also contributes to the rise in excessive Ca2+ influx. Numerous molecular pathways, including increases in the mitochondrial membrane potential and caspase (caspase3, caspase-8, and caspase-9) activations are induced by the increased cytosolic free Ca2+ concentrations. The apoptotic and neural death pathways are subsequently stimulated by the activations of molecular pathways. A new study found that the increases of TRPM2 expression levels were found in the apoptotic neuronal cells (An et al. 2019). Furthermore, it has been documented that a rise in TRPM2 expression caused neurons to death by necrosis, autophagy, and apoptosis (Shi et al. 2021). I will go over the rise in oxidative stress and neuronal cell death which are induced by TRPM2 channel expression in the oral presentation. According to evidence from the most recent research, the induction of neuronal cell death and oxidative stress in the neurons depends critically on the upregulation of TRPM2 expression.