Mitochondria as pharmacological targets in Down syndrome.

Autor: Valenti D; Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Bari, Italy., Braidy N; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Australia., De Rasmo D; Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Bari, Italy., Signorile A; Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Italy., Rossi L; Department of Clinical and Experimental Medicine, University of Pisa, Italy., Atanasov AG; Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland; Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria; Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria., Volpicella M; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy., Henrion-Caude A; INSERM U1163, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, GenAtlas Platform, 24 Boulevard du Montparnasse, 75015 Paris, France., Nabavi SM; Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran., Vacca RA; Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Council of Research, Bari, Italy. Electronic address: r.vacca@ibiom.cnr.it.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2018 Jan; Vol. 114, pp. 69-83. Date of Electronic Publication: 2017 Aug 31.
DOI: 10.1016/j.freeradbiomed.2017.08.014
Abstrakt: Mitochondria play a pivotal role in cellular energy-generating processes and are considered master regulators of cell life and death fate. Mitochondrial function integrates signalling networks in several metabolic pathways controlling neurogenesis and neuroplasticity. Indeed, dysfunctional mitochondria and mitochondrial-dependent activation of intracellular stress cascades are critical initiating events in many human neurodegenerative or neurodevelopmental diseases including Down syndrome (DS). It is well established that trisomy of human chromosome 21 can cause DS. DS is associated with neurodevelopmental delay, intellectual disability and early neurodegeneration. Recently, molecular mechanisms responsible for mitochondrial damage and energy deficits have been identified and characterized in several DS-derived human cells and animal models of DS. Therefore, therapeutic strategies targeting mitochondria could have great potential for new treatment regimens in DS. The purpose of this review is to highlight recent studies concerning mitochondrial impairment in DS, focusing on alterations of the molecular pathways controlling mitochondrial function. We will also discuss the effects and molecular mechanisms of naturally occurring and chemically synthetized drugs that exert neuroprotective effects through modulation of mitochondrial function and attenuation of oxidative stress. These compounds might represent novel therapeutic tools for the modulation of energy deficits in DS.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: