title: Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease that has no effective treatment up to date. Drug discovery tasks have been hampered due to the lack of knowledge in its molecular etiology together with the limited animal models for research. Recently, a motor neuron disease animal model has been developed using β-N-methylamino-L-alanine (L-BMAA), a neurotoxic amino acid related to the appearing of ALS. In the present work, the neuroprotective role of VP2.51, a small heterocyclic GSK-3 inhibitor, is analysed in this novel murine model together with the analysis of autophagy. VP2.51 daily administration for two weeks, starting the first day after L-BMAA treatment, leads to total recovery of neurological symptoms and prevents the activation of autophagic processes in rats. These results show that the L-BMAA murine model can be used to test the efficacy of new drugs. In addition, the results confirm the therapeutic potential of GSK-3 inhibitors, and specially VP2.51, for the disease-modifying future treatment of motor neuron disorders like ALS.
authors.affiliation: Departamento de Biología Animal II, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: de Munck
authors.affiliation: Centro de Investigaciones Biológicas-CSIC, Ramiro de Maetzu 9, Madrid, Spain.
authors.forename: Valle
authors.initials: V
authors.lastname: Palomo
authors.affiliation: Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Muñoz-Sáez
authors.affiliation: Centro de Investigaciones Biológicas-CSIC, Ramiro de Maetzu 9, Madrid, Spain.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Perez
authors.affiliation: Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Gómez-Miguel
authors.affiliation: Departamento de Biología Celular, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Solas
authors.affiliation: Centro de Investigaciones Biológicas-CSIC, Ramiro de Maetzu 9, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gil
authors.affiliation: Centro de Investigaciones Biológicas-CSIC, Ramiro de Maetzu 9, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez
authors.affiliation: Departamento de Biología Animal II, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Arahuetes
mesh_terms: D000818:Animals; D001343:Autophagy; D002460:Cell Line; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D051379:Mice; D016472:Motor Neuron Disease / Q000188:drug therapy*
chemical_list: D004791:Enzyme Inhibitors; D038362:Glycogen Synthase Kinase 3