Bexarotene targets autophagy and is protective against thromboembolic stroke in aged mice with tauopathy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Mikko T. Huuskonen, Sanna Loppi, Hiramani Dhungana, Velta Keksa-Goldsteine, Sighild Lemarchant, Paula Korhonen, Sara Wojciechowski, Eveliina Pollari, Piia Valonen, Juho Koponen, Akihiko Takashima, Gary Landreth, Gundars Goldsteins, Tarja Malm, Jari Koistinaho, Katja M. Kanninen

ABSTRACT

Stroke is a highly debilitating, often fatal disorder for which current therapies are suitable for only a minor fraction of patients. Discovery of novel, effective therapies is hampered by the fact that advanced age, primary age-related tauopathy or comorbidities typical to several types of dementing diseases are usually not taken into account in preclinical studies, which predominantly use young, healthy rodents. Here we investigated for the first time the neuroprotective potential of bexarotene, an FDA-approved agent, in a co-morbidity model of stroke that combines high age and tauopathy with thromboembolic cerebral ischemia. Following thromboembolic stroke bexarotene enhanced autophagy in the ischemic brain concomitantly with a reduction in lesion volume and amelioration of behavioral deficits in aged transgenic mice expressing the human P301L-Tau mutation. In in vitro studies bexarotene increased the expression of autophagy markers and reduced autophagic flux in neuronal cells expressing P301L-Tau. Bexarotene also restored mitochondrial respiration deficits in P301L-Tau neurons. These newly described actions of bexarotene add to the growing amount of compelling data showing that bexarotene is a potent neuroprotective agent, and identify a novel autophagy-modulating effect of bexarotene. More... »

PAGES

33176

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/srep33176

    DOI

    http://dx.doi.org/10.1038/srep33176

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1032069169

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27624652


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