Inhibition of transient receptor potential melastatin 7 (TRPM7) protects against Schwann cell trans-dedifferentiation and proliferation during Wallerian degeneration

Anim Cells Syst (Seoul). 2020 Aug 5;24(4):189-196. doi: 10.1080/19768354.2020.1804445.

Abstract

Irreversible peripheral neurodegenerative diseases such as diabetic peripheral neuropathy are becoming increasingly common due to rising rates of diabetes mellitus; however, no effective therapeutic treatments have been developed. One of main causes of irreversible peripheral neurodegenerative diseases is dysfunction in Schwann cells, which are neuroglia unique to the peripheral nervous system (PNS). Because homeostasis of calcium (Ca2+) and magnesium (Mg2+) is essential for Schwann cell dynamics, the regulation of these cations is important for controlling peripheral nerve degeneration and regeneration. Transient receptor potential melastatin 7 (TRPM7) is a non-selective ion (Ca2+ and Mg2+) channel that is expressed in Schwann cells. In the present study, we demonstrated in an ex vivo culture system that inhibition of TRPM7 during peripheral nerve degeneration (Wallerian degeneration) suppressed dedifferentiable or degenerative features (trans-dedifferentiation and proliferation) and conserved a differentiable feature of Schwann cells. Our results indicate that TRPM7 could be very useful as a molecular target for irreversible peripheral neurodegenerative diseases, facilitating discovery of new therapeutic methods for improving human health.

Keywords: Schwann cells; Transient receptor potential melastatin 7 (TRPM7); Wallerian degeneration; proliferation; trans-dedifferentiation.

Grants and funding

This work was supported by Basic Science Research Program through National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) [grant number 2018R1D1A1B07040282] and a grant from Kyung Hee University in 2019 (KHU-20191219).