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The role of TRPM channels in cell death

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Abstract

Transient receptor potential (TRP) channels of the melastatin-like family (TRPM) play critical roles in mediating cellular responses to a wide range of physiological stimuli that, under certain situations, can induce cell death. To date, two TRPM family members, TRPM2 and TRPM7, have been implicated directly as central components of cell death pathways. TRPM2, a Ca2+-permeant, non-selective cation channel, senses and responds to oxidative stress levels in the cell. TRPM7 is required for cell viability and has been proposed recently to mediate stress-induced cell death in the central nervous system. We review here the evidence for the involvement of these TRPM channels in cell death processes and discuss the mechanisms by which TRPM channel activation occurs. The ability to attenuate expression levels and functionality of these channels is necessary to understand the involvement of TRPM in cell death and we evaluate current approaches for modulation of TRPM channel function. Finally, we discuss the possibility that TRPM channels may provide therapeutic targets for degenerative diseases involving oxidative stress-related pathologies including diabetes and Alzheimer’s disease.

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Abbreviations

ADPR:

Adenine 5′-diphosphoribose

β-NAD+:

β-Nicotinamide-adenine dinucleotide

[Ca2+]i:

Intracellular free calcium ion concentration

H2O2:

Hydrogen peroxide

PARP:

Poly(ADP-ribose) polymerase

PKA:

Protein kinase A

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

TNF-α:

Tumour necrosis factor-α

TRPM2:

Melastatin-like transient receptor potential 2

TRPM2-S:

TRPM2 dominant negative splice variant

TRPM7:

Melastatin-like transient receptor potential 7

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Acknowledgements

Dr Elena Fonfria was the recipient of an EU Framework V Postdoctoral Fellowship under the project MCFH-2001-00746. We would like to thank Dr S. D. Skapper and Dr C. Rosin for their assistance with primary oligodendrocyte studies. We would like to thank Dr B. A. Miller and Dr W. Zhang for the supplying and permitting the use of TRPM2-S. In addition we thank Drs I. C. B. Marshall, and R. E. Kelsell for their kind help with development of the manuscript.

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Correspondence to S. McNulty.

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McNulty, S., Fonfria, E. The role of TRPM channels in cell death. Pflugers Arch - Eur J Physiol 451, 235–242 (2005). https://doi.org/10.1007/s00424-005-1440-4

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