Possible role of NF-kappaB and p53 in the glutamate-induced pro-apoptotic neuronal pathway.
Apoptosis is now recognized as an important component in many progressive and acute neurodegenerative diseases. Extracellular signals and intracellular mechanisms triggering and regulating apoptosis in neuronal cells are still a matter of investigation. Here we review data from our and other laboratories with the aim to elucidate the nature of some proteins which are known to be involved in cell cycle regulation as well as in promoting degeneration and apoptosis of neurons. The following molecules will be taken into consideration: NF-kappaB, p53, p21 and MSH2. These proteins are activated by neurotoxic experimental conditions which involve the stimulation of selective receptors for the excitatory aminoacid glutamate. Thus, we hypothesize their contribution to an intracellular pathway responsible for the glutamate-induced neuronal death. Identification of such mechanisms could be relevant for understanding the apoptosis associated with various neurodegenerative diseases as well as for developing novel strategies of pharmacological intervention.
Grilli
M
M
Schering-Plough Research Institute, San Raffaele Science Park, Milan, Italy.
Memo
M
M
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D018698:Glutamic Acid / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D016159:Tumor Suppressor Protein p53; D018698:Glutamic Acid