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Nitrones, Old Fellows for New Therapies in Ischemic Stroke

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Neuroprotective Therapy for Stroke and Ischemic Disease

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Ischemic stroke is suffered by millions of people worldwide, being the second cause of death in 2012. To date, only recombinant tissue plasminogen activator and thrombectomy, as first-line recanalization approaches, are the only treatments approved for ischemic stroke therapy. Nevertheless, the low number of patients who can benefit from this treatment, as well as the limited beneficial outcome, even if proper recanalization rates are achieved, make evident the need for complementary therapeutic approaches. Among them, the neuroprotection strategy appeared as a promising approach which led to the development of drugs targeting distinct steps of the biochemical pathways that take place during and after the ischemic insult. However, no effective translation from preclinical studies to clinical use has been achieved until now, rising thus doubts about the suitability of the neuroprotection therapeutic strategy. Regarding the intrinsic complexity of ischemic stroke, pleiotropy has been proposed as a key issue, and nitrones, known to act as radical traps, have arisen as interesting drug candidates. From its widely known antioxidant behavior, new mechanisms of action have been proposed based on reported evidence. In this chapter, nitrones pleiotropy is reviewed. Specific results of nitrones developed by our group are reported and discussed.

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Acknowledgments

We are indebted to Ph.D. D.J. Hadjipavlou-Litina for the in vitro antioxidants experiments and Ms. M. Gómez-Calcerrada for her assistance. This work was supported by the Institute of Health Carlos III from the Spanish Ministry of Economy and Competitiveness (MINECO) with the grant number PI14/00705 (State Plan), and the funding from FEDER grants. JMC and MC thank MINECO grants SAF2012-33304 and SAF2015-65586-R, European Union (COST Action 1103) and Universidad Camilo José Cela, for support.

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Authors and Affiliations

  1. Laboratory of Medicinal Chemistry, Institute of General Organic Chemistry (CSIC), Juan de la Cierva 3, Madrid, 28006, Spain

    Alejandro Escobar-Peso, Mourad Chioua & José Marco-Contelles

  2. Department of Investigation, Hospital Ramón y Cajal, IRYCIS, Madrid, 28034, Spain

    Valerio Frezza, Emma Martínez-Alonso & Alberto Alcázar

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  1. Alejandro Escobar-Peso
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  2. Mourad Chioua
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  3. Valerio Frezza
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  4. Emma Martínez-Alonso
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  5. José Marco-Contelles
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  6. Alberto Alcázar
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Correspondence to Alberto Alcázar .

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Editors and Affiliations

  1. Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Paul A. Lapchak

  2. Loma Linda University School of Medicine, Loma Linda, California, USA

    John H. Zhang

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Escobar-Peso, A., Chioua, M., Frezza, V., Martínez-Alonso, E., Marco-Contelles, J., Alcázar, A. (2017). Nitrones, Old Fellows for New Therapies in Ischemic Stroke. In: Lapchak, P., Zhang, J. (eds) Neuroprotective Therapy for Stroke and Ischemic Disease. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-45345-3_9

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