Protein synthesis inhibitors, gene superinduction and memory: too little or too much protein?
To date, the effects of protein synthesis inhibitors (PSI) in learning and memory processes have been attributed to translational arrest and consequent inhibition of de novo protein synthesis. Here we argue that amnesia produced by PSI can be the direct result of their abnormal induction of mRNA-a process termed gene superinduction. This action exerted by PSI involves an abundant and prolonged accumulation of mRNA transcripts of genes that are normally transiently induced. We summarize experimental evidence for the multiple mechanisms and signaling pathways mediating gene superinduction and consider its relevance for PSI-induced amnesia. This mechanistic alternative to protein synthesis inhibition is compared to models of electroconvulsive seizures and fragilexsyndrome associated with enhanced mRNA/protein levels and cognitive deficits.
Radulovic
Jelena
J
Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL 60611, USA. j-radulovic@northwestern.edu
Tronson
Natalie C
NC
D000647:Amnesia / Q000139:chemically induced / Q000235:genetics; D000841:Anisomycin / Q000008:administration & dosage / Q000009:adverse effects*; D053476:Extinction, Biological; D005786:Gene Expression Regulation / Q000235:genetics; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D010750:Phosphoproteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D000841:Anisomycin