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.