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Miquel 2014 Free Radic Biol Med

From Bioblast
Publications in the MiPMap
Miquel E, Cassina A, Martínez-Palma L, Souza JM, Bolatto C, Rodríguez-Bottero S, Logan A, Smith RA, Murphy MP, Barbeito L, Radi R, Cassina P (2014) Neuroprotective effects of the mitochondria-targeted antioxidant MitoQ in a model of inherited amyotrophic lateral sclerosis. Free Radic Biol Med 70:204-13.

» PMID: 24582549

Miquel E, Cassina AM, Martinez-Palma L, Souza JM, Bolatto C, Rodriguez-Bottero S, Logan A, Smith RA, Murphy MP, Barbeito L, Radi R, Cassina P (2014) Free Radic Biol Med

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motor neuron degeneration that ultimately results in progressive paralysis and death. Growing evidence indicates that mitochondrial dysfunction and oxidative stress contribute to motor neuron degeneration in ALS. To further explore the hypothesis that mitochondrial dysfunction and nitroxidative stress contribute to disease pathogenesis at the in vivo level, we assessed whether the mitochondria-targeted antioxidant [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4- cyclohexadien-1-yl)decyl]triphenylphosphonium methanesulfonate (MitoQ) can modify disease progression in the SOD1G93A mouse model of ALS. To do this, we administered MitoQ (500µM) in the drinking water of SOD1G93A mice from a time when early symptoms of neurodegeneration become evident at 90 days of age until death. This regime is a clinically plausible scenario and could be more easily translated to patients as this corresponds to initiating treatment of patients after they are first diagnosed with ALS. MitoQ was detected in all tested tissues by liquid chromatography/mass spectrometry after 20 days of administration. MitoQ treatment slowed the decline of mitochondrial function, both in the spinal cord and quadriceps muscle as measured by high-resolution respirometry. Importantly, nitroxidative markers and pathological signs in the spinal cord of MitoQ-treated animals were markedly reduced and neuromuscular junctions were recovered associated to a significant increase in hind-limb strength. Finally, MitoQ treatment significantly prolonged the lifespan of SOD1G93A mice. Our results support a role for mitochondrial nitroxidative damage and dysfunction in the pathogenesis of ALS and suggest that mitochondria-targeted antioxidants may be of pharmacological use for ALS treatment. Keywords: Amyotrophic Lateral Sclerosis, Free radicals, Nitroxidative stress, Antioxidants, Mitochondria, MitoQ, Uncoupling control ratio

O2k-Network Lab: UY Montevideo Radi R


Labels: MiParea: Respiration  Pathology: Neurodegenerative 

Organism: Mouse  Tissue;cell: Skeletal muscle, Nervous system  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS, ET  Pathway: NS, ROX  HRR: Oxygraph-2k