TRPMs and neuronal cell death.
Death of CNS neurons during acute injury occurs as a result of a complex combination of excitotoxicity, necrosis, apoptosis, oedema and inflammatory reactions. Neuroprotection via glutamate receptor blockade or antioxidant or anti-inflammatory therapy have not proven effective in the clinical treatment of brain damage due to narrow therapeutic windows, poor pharmacokinetics or blockade of the signalling essential for normal excitatory neurotransmission and neuronal survival. Recent work in neuronal biochemistry, genomics and proteomics has increased understanding of the molecular organization of the excitatory synapse and the neuronal postsynaptic density. Transient receptor potential (TRP) channels are an exciting new family of cation channels that are highly expressed in the brain. Several members can be induced by oxidative stress and oxygen free radicals, both of which play important roles in neurodegeneration. Recent work has indicated that members of the melastatin subfamily (TRPM) of TRP proteins, particularly TRPM7 and TRPM2, may play key roles in neuronal death that is activated by oxidative stress and downstream from excitotoxic signal pathways. This discovery provides an exiting new avenue for research into the pathophysiology and treatment of acute neurodegeneration.
Aarts
Michelle M
MM
Applied and Interventional Research and Division of Neurosurgery, Toronto Western Research Institute, W4-325, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada.
Tymianski
Michael
M
D002118:Calcium / Q000502:physiology; D016923:Cell Death / Q000187:drug effects*; D002493:Central Nervous System Diseases / Q000503:physiopathology*; D005947:Glucose / Q000172:deficiency; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species / Q000378:metabolism; D050053:TRPM Cation Channels / Q000502:physiology*
D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D005947:Glucose; D002118:Calcium