Glutamate, glutamate receptors, and downstream signaling pathways.
Glutamate is a nonessential amino acid, a major bioenergetic substrate for proliferating normal and neoplastic cells, and an excitatory neurotransmitter that is actively involved in biosynthetic, bioenergetic, metabolic, and oncogenic signaling pathways. Glutamate signaling activates a family of receptors consisting of metabotropic glutamate receptors (mGluRs) and ionotropic glutamate receptors (iGluRs), both of which have been implicated in chronic disabling brain disorders such as Schizophrenia and neurodegenerative diseases like Alzheimer's, Parkinson's, and multiple sclerosis. In this review, we discuss the structural and functional relationship of mGluRs and iGluRs and their downstream signaling pathways. The three groups of mGluRs, the associated second messenger systems, and subsequent activation of PI3K/Akt, MAPK, NFkB, PLC, and Ca/CaM signaling systems will be discussed in detail. The current state of human mGluR1a as one of the most important isoforms of Group I-mGluRs will be highlighted. The lack of studies on the human orthologues of mGluRs family will be outlined. We conclude that upon further study, human glutamate-initiated signaling pathways may provide novel therapeutic opportunities for a variety of non-malignant and malignant human diseases.
['Willard|Stacey S|SS|', 'Koochekpour|Shahriar|S|']
D000595:Amino Acid Sequence D002118:Calcium D020013:Calcium Signaling D048049:Extracellular Signal-Regulated MAP Kinases D018698:Glutamic Acid D006801:Humans D008954:Models, Biological D008969:Molecular Sequence Data D016328:NF-kappa B D009369:Neoplasms D019869:Phosphatidylinositol 3-Kinases D043562:Receptors, G-Protein-Coupled D017470:Receptors, Glutamate D016415:Sequence Alignment D015398:Signal Transduction D010738:Type C Phospholipases
Glutamate mGluR iGluR GRM1a signaling.