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Título
Protective effects of synthetic kynurenines on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice
Autor
Año del Documento
2011
Descripción
Producción Científica
Documento Fuente
Brain Research Bulletin, Mayo 2011, vol. 85, n. 3-4, p. 133-140
Abstract
Mitochondrial complex I inhibition is thought to underlie the neurodegenerative process in Parkinson's disease (PD). Moreover, an overproduction of nitric oxide due to both cytosolic (iNOS) and mitochondrial (i-mtNOS) inducible nitric oxide synthases causes free radicals generation and oxidative/nitrosative stress, contributing to mitochondrial dysfunction and neuronal cell death. Looking for active molecules against mitochondrial dysfunction and inflammatory response in PD, we show here the effects of four synthetic kynurenines in the MPTP model of PD in mice. After MPTP administration, mitochondria from substantia nigra and, in a lesser extent, from striatum showed a significant increase in i-mtNOS activity, nitric oxide production, oxidative stress, and complex I inhibition. The four kynurenines assayed counteracted the effects of MPTP, reducing iNOS/i-mtNOS activity, and restoring the activity of the complex I. Consequently, the cytosolic and mitochondrial oxidative/nitrosative stress returned to control values. The results suggest that the kynurenines here reported represent a family of synthetic compounds with neuroprotective properties against PD, and that they can serve as templates for the design of new drugs able to target the mitochondria.
ISSN
0361-9230
Revisión por pares
SI
Patrocinador
This work was partially supported by grants RD06/0013/0008 and RD06/0013/1023 (RETICEF); SAF2009-09053 and SAF2005-07991-C02-01/02 from the Ministerio de Educación (Spain); PI08-1644 from the ISCIII (Spain), and P07-CTS-03135 from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (Spain).
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
embargoedAccess
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