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Small GSK-3 inhibitor shows efficacy in a motor neuron disease murine model modulating autophagy

AuthorsDe Munck, E.; Palomo, Valle ; Muñoz-Sáez, E.; Pérez Fernández, Daniel Ignacio ; Gómez-Miguel, Begoña; Solas, M. Teresa; Gil, Carmen ; Martínez, Ana ; Arahuetes, Rosa Mª
Issue Date15-Sep-2016
PublisherPublic Library of Science
CitationPLoS ONE 11(9): e0162723 (2016)
AbstractAmyotrophic 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-Nmethylamino-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. VP2.51daily 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-BMAAmurine model can be used to test the efficacy of new drugs. In addition, the results confirmthe therapeutic potential of GSK-3 inhibitors, and specially VP2.51, for the disease-modifying future treatment of motor neuron disorders like ALS.
Description16 p.-4 fig.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0162723
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