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

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ID: 34701
2016
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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.
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munck2016smallplos Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Estefanía de Munck, Valle Palomo, Emma Muñoz-Sáez, Daniel I Perez, Begoña Gómez-Miguel, M Teresa Solas, Carmen Gil, Ana Martínez, Rosa M Arahuetes
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Journal PloS one
Year 2016
DOI
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URL
http://europepmc.org/articles/PMC5025054?pdf=render
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