Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems
Herrando-Grabulosa, Mireia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Mulet, Roger (Anaxomics Biotech)
Pujol, Albert (Institut de Recerca Biomèdica de Lleida)
Mas, José Manuel (Anaxomics Biotech)
Navarro, X. (Xavier) (Xavier) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Aloy, Patrick (Institut de Recerca Biomèdica de Lleida)
Coma, Mireia (Anaxomics Biotech)
Casas Louzao, Caty (Universitat Autònoma de Barcelona. Institut de Neurociències)

Fecha:	2016
Resumen:	Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology), we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Spinal cord ; Microglial cells ; Systems biology ; Amyotrophic lateral sclerosis ; Drug screening ; Drug therapy ; Glutamate ; Protein interaction networks
Publicado en:	PloS one, Vol. 11, Num. 1 (January 2016) , p. 1-17, ISSN 1932-6203

DOI: 10.1371/journal.pone.0147626
PMID: 26807587

17 p, 5.8 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Neurociències (INc)
Artículos > Artículos de investigación
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