RT info:eu-repo/semantics/article
T1 Protective effects of synthetic kynurenines on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice
A1 Acuña Castroviejo, Darío
A1 Tapias Molina, Victor
A1 López, Luis C.
A1 Doerrier, Carolina
A1 Camacho, Encarnación
A1 Carrión, María D.
A1 Mora, Francisco
A1 Espinosa, Antonio
A1 Escames, Germaine
AB 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.
SN 0361-9230
YR 2011
FD 2011
LK https://uvadoc.uva.es/handle/10324/63877
UL https://uvadoc.uva.es/handle/10324/63877
LA eng
NO Brain Research Bulletin, Mayo 2011, vol. 85, n. 3-4, p. 133-140
NO Producción Científica
DS UVaDOC
RD 04-abr-2025