Effect of mitochondrial transcription factor a overexpression on motor neurons in amyotrophic lateral sclerosis model mice

Journal of Neuroscience Research
Nobutoshi MorimotoKoji Abe

Abstract

Increasing evidence indicates that oxidative stress is an important mechanism underlying motor neuron (MN) degeneration in amyotrophic lateral sclerosis (ALS). Mitochondrial DNA (mtDNA) is highly susceptible to oxidative damage and has little potential for repair, although mitochondrial transcription factor A (TFAM) plays essential roles in maintaining mitochondrial DNA by reducing oxidative stress, promoting mtDNA transcription, and regulating mtDNA copy number. To analyze a possible therapeutic effect of TFAM on ALS pathology, double transgenic mice overexpressing G93A mutant SOD1 (G93ASOD1) and human TFAM (hTFAM) were newly generated in the present study. Rotarod scores were better in G93ASOD1/hTFAM double-Tg mice than G93ASOD1 single-Tg mice at an early symptomatic stage, 15 and 16 weeks of age, with a 10% extension of the onset age in double-Tg mice. The number of surviving MNs was 30% greater in double-Tg mice with end-stage disease, at 19 weeks, with remarkable reductions in the amount of the oxidative stress marker 8-OHdG and the apoptotic marker cleaved caspase 3 and with preserved COX1 expression. Double-immunofluorescence study showed that hTFAM was expressed specifically in MNs and microglia in the spinal cords of d...Continue Reading

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Citations

Aug 29, 2012·Oxidative Medicine and Cellular Longevity·M Isabel González Siso, M Esperanza Cerdán
Dec 3, 2013·Physiology & Behavior·Susan E SmittkampJohn A Stanford
Nov 14, 2012·Journal of Neuropathology and Experimental Neurology·Nadine ThauSusanne Petri
Jul 23, 2015·Molecular Neurobiology·Ewa NiedzielskaMałgorzata Filip
Dec 5, 2012·Biochemical and Biophysical Research Communications·Takako MatsudaEtsuko T Matsuura
Sep 14, 2014·Journal of Bioenergetics and Biomembranes·Juan Carlos Corona, Michael R Duchen
May 7, 2015·American Journal of Physiology. Endocrinology and Metabolism·Krish ChandrasekaranJames W Russell
Sep 1, 2021·Life Science Alliance·Nina A BonekampNils-Göran Larsson

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