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

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Munk, Estefanía de and Palomo, Valle and Muñoz Sáez, Emma and Pérez, Daniel I. and Gómez Miguel, Begoña and Solas Alados, Mª Teresa and Gil, Carmen and Martínez, Ana and Arahuetes Portero, Rosa María (2016) Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy. Plos One, 11 (9). ISSN 1932-6203

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Official URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162723



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-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. VP2.51 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.


Item Type:Article
Uncontrolled Keywords:Autophagic cell death, Spinal cord, Motor neuron diseases, Animal mode disease
Subjects:Medical sciences > Biology > Animal physiology
Medical sciences > Biology > Neurosciences
ID Code:41049
Deposited On:02 Feb 2017 12:57
Last Modified:07 Feb 2017 12:57

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