Oncogenes on my mind: ERK and MTOR signaling in cognitive diseases.
Defects in rat sarcoma viral oncogene homolog (RAS)-extracellular signal regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)-mammalian target of rapamycin (MTOR) signaling pathways have recently been shown to cause several genetic disorders classified as neuro-cardio-facial-cutaneous (NCFC) and Hamartoma syndromes. Although these pathways are well-known players in cell proliferation and cancer, their role in cognitive function is less appreciated. Here, we focus on the cognitive problems associated with mutations in the RAS-ERK and PI3K-MTOR signaling pathways and on the underlying mechanisms revealed by recent animal studies. Cancer drugs have been shown to reverse the cognitive deficits in mouse models of NCFC and Hamartoma syndromes, raising hopes for clinical trials.
Krab
Lianne C
LC
Department of Neuroscience, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands.
Goorden
Susanna M I
SM
Elgersma
Ype
Y
D000818:Animals; D003072:Cognition Disorders / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000378:metabolism; D009857:Oncogenes / Q000502:physiology*; D014176:Protein Biosynthesis / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics; D058570:TOR Serine-Threonine Kinases
D018377:Neurotransmitter Agents; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D016283:Proto-Oncogene Proteins p21(ras)