JOURNAL ARTICLE
REVIEW

TRPM2 cation channels, oxidative stress and neurological diseases: where are we now?

Mustafa Nazıroğlu
Neurochemical Research 2011, 36 (3): 355-66
21140288
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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
21140288
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"