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Neuroprotective properties of mitochondria-targeted antioxidants of the SkQ-type

  • Nickolay K. Isaev EMAIL logo , Elena V. Stelmashook , Elisaveta E. Genrikhs , Galina A. Korshunova , Natalya V. Sumbatyan , Marina R. Kapkaeva and Vladimir P. Skulachev
Published/Copyright: August 25, 2016

Abstract

In 2008, using a model of compression brain ischemia, we presented the first evidence that mitochondria-targeted antioxidants of the SkQ family, i.e. SkQR1 [10-(6′-plastoquinonyl)decylrhodamine], have a neuroprotective action. It was shown that intraperitoneal injections of SkQR1 (0.5–1 μmol/kg) 1 day before ischemia significantly decreased the damaged brain area. Later, we studied in more detail the anti-ischemic action of this antioxidant in a model of experimental focal ischemia provoked by unilateral intravascular occlusion of the middle cerebral artery. The neuroprotective action of SkQ family compounds (SkQR1, SkQ1, SkQTR1, SkQT1) was manifested through the decrease in trauma-induced neurological deficit in animals and prevention of amyloid-β-induced impairment of long-term potentiation in rat hippocampal slices. At present, most neurophysiologists suppose that long-term potentiation underlies cellular mechanisms of memory and learning. They consider inhibition of this process by amyloid-β1-42 as an in vitro model of memory disturbance in Alzheimer’s disease. Further development of the above studies revealed that mitochondria-targeted antioxidants could retard accumulation of hyperphosphorylated τ-protein, as well as amyloid-β1-42, and its precursor APP in the brain, which are involved in developing neurodegenerative processes in Alzheimer’s disease.

Acknowledgments

This work was done with financial support from the Russian Science Foundation (Project no. 16-15-10108, section ‘SkQs decrease brain damage after traumatic brain injury’, and no. 14-24-00107, section ‘SkQs decrease brain damage after ischemia’ and ‘SkQ in models of Alzheimer’s disease’).

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Received: 2016-6-10
Accepted: 2016-7-13
Published Online: 2016-8-25
Published in Print: 2016-12-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

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