title: Inhibition of Protein Phosphatase 2A: Focus on the Glutamatergic System.
abstract: In a recent review published in Molecular Neurobiology, Kamat and colleagues (Mol Neurobiol. 2014 Dec;50(3):852-65) highlighted the cellular and molecular mechanisms involved in Okadaic acid (OKA)-induced neurotoxicity. In this review, the authors underline a wide range of pathological signaling pathways involved in OKA-induced neurotoxicity; however, the role of glutamate was only briefly described. We believe that the hyperactivation of the glutamatergic system is a key pathophysiological player in OKA-induced neurotoxicity and deserves serious attention. In this commentary, we propose an integrative model linking glutamate and PP2A and put forward some unanswered questions.
authors.affiliation: Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul (UFRGS), 2600 Ramiro Barcelos Street, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Zimmer
authors.affiliation: Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Antoine
authors.initials: A
authors.lastname: Leuzy
authors.affiliation: Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul (UFRGS), 2600 Ramiro Barcelos Street, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Diogo O
authors.initials: DO
authors.lastname: Souza
authors.affiliation: Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul (UFRGS), 2600 Ramiro Barcelos Street, 90035-003, Porto Alegre, RS, Brazil. roskaportela@gmail.com.
authors.forename: Luis V
authors.initials: LV
authors.lastname: Portela
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D019319:Okadaic Acid / Q000494:pharmacology; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D019319:Okadaic Acid; D018698:Glutamic Acid; D054648:Protein Phosphatase 2
keywords: Excitotoxicity; Glutamate; Okadaic acid; Protein phosphatase 2A; Tau hyperphosphorylation