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Role of oxidative stress and calcium regulation in Duchenne muscular dystrophy: pharmacological investigations

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Defense Thèse de doctorat : Univ. Genève, 2013 - Sc. 4607 - 2013/10/24
Abstract Duchenne Muscular Dystrophy (DMD) is the most common and most severe myopathy. Currently, no cure exists for DMD and novel pharmacotherapy holds the promise of being the fastest route for reaching the patients until a curative genetic therapy is delivered. Towards this end, three drug candidates were evaluated in DMD models. The first was doxorubicin which inhibited phospholipase A2 activity and reduced Ca2+ influx through stretch-activated channels, both reported to be overactive in dystrophic cells. Dystrophic muscles treated with doxorubicin were protected from damaging eccentric contractions. We have also tested the classical NADPH oxidase inhibitor apocynin and its synthetic dimer, diapocynin. Our in vitro and in vivo results show that diapocynin holds a superior therapeutic potential. In conclusion, the work presented in this thesis presents novel drug candidates that can be developed further as potential pharmacotherapeutic treatment for DMD. It also sheds light on the pathways involved in DMD pathogenesis.
Keywords Duchenne muscualr dystrophyStretch activated channelsStore operated channelsPhospholipase A2NADPH oxidaseDoxorubicinApocyninDiapocyninMuscle
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URN: urn:nbn:ch:unige-321331
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ISMAIL, Hesham. Role of oxidative stress and calcium regulation in Duchenne muscular dystrophy: pharmacological investigations. Université de Genève. Thèse, 2013. https://archive-ouverte.unige.ch/unige:32133

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Deposited on : 2013-12-16

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