Redox regulation of neuronal survival mediated by electrophilic compounds.
The importance of phosphorylation of key threonine, serine and tyrosine residues is a well known essential feature of many signal transduction pathways. A similar, highly conserved redox reaction involving cysteine thiols is now emerging as an important regulator of protein function. An example of this redox regulation is S-nitrosylation (the transfer of a nitric oxide group to a key protein thiol). Here, we review the chemical biology of an additional class of drugs, electrophiles (electron-deficient carbon centers), that react with key protein thiols, and provide insights into a broader class of reactions implicated in redox signaling. Interestingly, certain electrophilic compounds, including endogenous metabolites and natural products, seem to have neuroprotective effects, and this has resulted in the development of neuroprotective electrophilic drugs, including prostaglandin derivatives and hydroquinones, that exert their action through activating antioxidant-signaling cascades.
Satoh
Takumi
T
Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka 020-8551, Japan. tsatoh@iwate-u.ac.jp
Lipton
Stuart A
SA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003545:Cysteine / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000975:Antioxidants; D013438:Sulfhydryl Compounds; D003545:Cysteine