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PLoS One. 2016 Sep 15;11(9):e0162723. doi: 10.1371/journal.pone.0162723. eCollection 2016.

Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy.

Author information

1
Departamento de Biología Animal II, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain.
2
Centro de Investigaciones Biológicas-CSIC, Ramiro de Maetzu 9, Madrid, Spain.
3
Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain.
4
Departamento de Biología Celular, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain.

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.

PMID:
27631495
PMCID:
PMC5025054
DOI:
10.1371/journal.pone.0162723
[Indexed for MEDLINE]
Free PMC Article

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