caa a22 4500 445314443 CHVBK 20180317142641.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s11095-011-0476-8 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0476-8 Novel Therapies Targeting Inner Mitochondrial Membrane—From Discovery to Clinical Development [Elektronische Daten] [Hazel Szeto, Peter Schiller] ABSTRACT: Mitochondrial oxidative stress and dysfunction have been implicated in the aging process and in numerous chronic diseases. The need for therapies that can protect and/or improve mitochondrial function is obvious. However, the development of mitoprotective drugs has been hampered by a number of challenges, and there are at present no approved therapies for mitochondrial dysfunction. This article describes the original discovery, preclinical development, and clinical development of a novel class of small peptide molecules that selectively target the inner mitochondrial membrane and protect mitochondrial function. These compounds have the potential to be a paradigm-shifting approach to the treatment of mitochondrial dysfunction, which underlies many common diseases, including cardiorenal, neurologic, and metabolic disorders. Springer Science+Business Media, LLC, 2011 ischemia-reperfusion injury nationallicence metabolic disorders nationallicence neurodegenerative diseases nationallicence oxidative stress nationallicence Szeto-Schiller peptides nationallicence ATP : adenosine triphosphate nationallicence BBB : blood-brain barrier nationallicence CypD : cyclophilin D nationallicence Cyt c : cytochrome c nationallicence ETC : electron transport chain nationallicence IMM : inner mitochondrial membrane nationallicence iv : intravenous nationallicence MCAT : overexpression of catalase targeted to mitochondria nationallicence MPP+ : 1-methyl-4-phenylpyridium nationallicence MPT : mitochondrial permeability transition nationallicence MPTP : 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine nationallicence OMM : outer mitochondrial membrane nationallicence ROS : reactive oxygen species nationallicence sc : subcutaneous nationallicence SOD : superoxide dismutase nationallicence TPP+ : triphenylphosphonium ion nationallicence Szeto Hazel Department of Pharmacology, Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, 10021, New York, New York, USA aut Schiller Peter Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, Montreal, Quebec, Canada aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2669-2679 0724-8741 28:11<2669 2011 28 11095 https://doi.org/10.1007/s11095-011-0476-8 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0476-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Szeto Hazel Department of Pharmacology, Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, 10021, New York, New York, USA aut NATIONALLICENCE 700 1- Schiller Peter Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, Montreal, Quebec, Canada aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2669-2679 0724-8741 28:11<2669 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer