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TRPM2 Cation Channels, Oxidative Stress and Neurological Diseases: Where Are We Now?

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Abstract

The Na+ and Ca2+-permeable melastatin related transient receptor potential 2 (TRPM2) channels can be gated either by ADP-ribose (ADPR) in concert with Ca2+ or by hydrogen peroxide (H2O2), an experimental model for oxidative stress, binding to the channel’s enzymatic Nudix domain. Since the mechanisms that lead to TRPM2 gating in response to ADPR and H2O2 are not understood in neuronal cells, I summarized previous findings and important recent advances in the understanding of Ca2+ influx via TRPM2 channels in different neuronal cell types and disease processes. Considering that TRPM2 is activated by oxidative stress, mediated cell death and inflammation, and is highly expressed in brain, the channel has been investigated in the context of central nervous system. TRPM2 plays a role in H2O2 and amyloid β-peptide induced striatal cell death. Genetic variants of the TRPM2 gene confer a risk of developing Western Pacific amyotropic lateral sclerosis and parkinsonism-dementia complex and bipolar disorders. TRPM2 also contributes to traumatic brain injury processes such as oxidative stress, inflammation and neuronal death. There are a limited number of TRPM2 channel blockers and they seem to be cell specific. For example, ADPR-induced Ca2+ influx in rat hippocampal cells was not blocked by N-(p-amylcinnomoyl)anthralic acid (ACA), the IP3 receptor inhibitor 2-aminoethoxydiphenyl borate or PLC inhibitor flufenamic acid (FFA). However, the Ca2+ entry in rat primary striatal cells was blocked by ACA and FFA. In conclusion TRPM2 channels in neuronal cells can be gated by either ADPR or H2O2. It seems to that the exact relationship between TRPM2 channels activation and neuronal cell death still remains to be determined.

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Abbreviations

2-APB:

2-Aminoethoxydiphenyl borate.

ACA:

N-(p-amylcinnomoyl)anthranilic acid

AD:

Alzheimer’s disease

ADPR:

Adenosine diphosphatase ribose

CHO:

Chinese hamster ovary

CNS:

Central nervous system

DRG:

Dorsal rood ganglion

FFA:

Flufenamic acid

HEK:

Human embryonic kidney

PARG:

Poly (ADP-ribose) glycohydrolase

PARP:

Poly(ADP-ribose) polymerase

PD:

Parkinson disease

PKC:

Protein kinase C

ROS:

Reactive oxygen species

TNF-α:

Tumor necrosis factor alpha

TRP:

Transient receptor potential

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Acknowledgments

The author wishes thanks to Prof. Dr. James W. Putney (Calcium Regulation Section, NIEHS, USA) and Ercan Sözbir (Department of Biophysics, SDU, Isparta, Turkey) for polishing English of the paper and preparation of Figures, respectively.

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  1. Neuroscience Research Center, Süleyman Demirel University, Isparta, Turkey

    Mustafa Nazıroğlu

  2. Department of Biophysics, Medical Faculty, Süleyman Demirel University, 32260, Isparta, Turkey

    Mustafa Nazıroğlu

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Correspondence to Mustafa Nazıroğlu.

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Nazıroğlu, M. TRPM2 Cation Channels, Oxidative Stress and Neurological Diseases: Where Are We Now?. Neurochem Res 36, 355–366 (2011). https://doi.org/10.1007/s11064-010-0347-4

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