title: TRPM2 cation channels, oxidative stress and neurological diseases: where are we now?
abstract: The Na+ and Ca(2+)-permeable melastatin related transient receptor potential 2 (TRPM2) channels can be gated either by ADP-ribose (ADPR) in concert with Ca(2+) or by hydrogen peroxide (H(2)O(2)), 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 H(2)O(2) are not understood in neuronal cells, I summarized previous findings and important recent advances in the understanding of Ca(2+) 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 H(2)O(2) 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 Ca(2+) influx in rat hippocampal cells was not blocked by N-(p-amylcinnomoyl)anthralic acid (ACA), the IP(3) receptor inhibitor 2-aminoethoxydiphenyl borate or PLC inhibitor flufenamic acid (FFA). However, the Ca(2+) 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 H(2)O(2). It seems to that the exact relationship between TRPM2 channels activation and neuronal cell death still remains to be determined.
authors.affiliation: Neuroscience Research Center, Süleyman Demirel University, Isparta, Turkey. mnaziroglu@med.sdu.edu.tr
authors.forename: Mustafa
authors.initials: M
authors.lastname: Nazıroğlu
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D009243:NAD / Q000378:metabolism; D009422:Nervous System Diseases / Q000503:physiopathology*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D020033:Protein Isoforms; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D002118:Calcium