Mitochondria-Targeted Drugs

被引:145
作者
Zinovkin, Roman A. [1 ,2 ,3 ]
Zamyatnin, Andrey A., Jr. [1 ,2 ]
机构
[1] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119991, Russia
[2] Sechenov First Moscow State Med Univ, Inst Mol Med, Trubetskaya Str 8, Moscow 119991, Russia
[3] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow, Russia
基金
俄罗斯科学基金会; 俄罗斯基础研究基金会;
关键词
Mitochondria; targeted drug delivery; uncouplers of oxidative phosphorylation; reactive oxygen species; antioxidants; metabolic syndrome; RESPONSE SYNDROME SIRS; HUMAN SKELETAL-MUSCLE; INFLAMMATORY RESPONSE; ANTIOXIDANT MITOQ; ALZHEIMERS-DISEASE; HUMAN NEUTROPHILS; NOX FAMILY; LIFE-SPAN; OXIDATIVE-PHOSPHORYLATION; ELECTRON-TRANSPORT;
D O I
10.2174/1874467212666181127151059
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Targeting of drugs to the subcellular compartments represents one of the modern trends in molecular pharmacology. The approach for targeting mitochondria was developed nearly 50 years ago, but only in the last decade has it started to become widely used for delivering drugs. A number of pathologies are associated with mitochondrial dysfunction, including cardiovascular, neurological, inflammatory and metabolic conditions. Objective: This mini-review aims to highlight the role of mitochondria in pathophysiological conditions and diseases, to classify and summarize our knowledge about targeting mitochondria and to review the most important preclinical and clinical data relating to the antioxidant lipophilic cations MitoQ and SkQ1. Methods: This is a review of available information in the PubMed and Clinical Trials databases (US National Library of Medicine) with no limiting period. Results and Conclusion: Mitochondria play an important role in the pathogenesis of many diseases and possibly in aging. Both MitoQ and SkQ1 have shown many beneficial features in animal models and in a few completed clinical trials. More clinical trials and research efforts are needed to understand the signaling pathways influenced by these compounds. The antioxidant lipophilic cations have great potential for the treatment of a wide range of pathologies.
引用
收藏
页码:202 / 214
页数:13
相关论文
共 138 条
[11]   Systemic inflammatory response syndrome (SIRS) Where did it come from and is it still relevant today? [J].
Balk, Robert A. .
VIRULENCE, 2014, 5 (01) :20-26
[12]  
Beal M Flint, 2007, Novartis Found Symp, V287, P183
[13]  
BEAL MF, 1993, J NEUROSCI, V13, P4181
[14]   The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology [J].
Bedard, Karen ;
Krause, Karl-Heinz .
PHYSIOLOGICAL REVIEWS, 2007, 87 (01) :245-313
[15]   The Mitochondrial-Targeted Compound SS-31 Re-Energizes Ischemic Mitochondria by Interacting with Cardiolipin [J].
Birk, Alexander V. ;
Liu, Shaoyi ;
Soong, Yi ;
Mills, William ;
Singh, Pradeep ;
Warren, J. David ;
Seshan, Surya V. ;
Pardee, Joel D. ;
Szeto, Hazel H. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2013, 24 (08) :1250-1261
[16]   Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity [J].
Boudina, S ;
Sena, S ;
O'Neill, BT ;
Tathireddy, P ;
Young, ME ;
Abel, ED .
CIRCULATION, 2005, 112 (17) :2686-2695
[17]   The Effect of MitoQ on Aging-Related Biomarkers: A Systematic Review and Meta-Analysis [J].
Braakhuis, Andrea J. ;
Nagulan, Rohith ;
Somerville, Vaughan .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2018, 2018
[18]   Mitochondrial function as a therapeutic target in heart failure [J].
Brown, David A. ;
Perry, Justin B. ;
Allen, Mitchell E. ;
Sabbah, Hani N. ;
Stauffer, Brian L. ;
Shaikh, Saame Raza ;
Cleland, John G. F. ;
Colucci, Wilson S. ;
Butler, Javed ;
Voors, Adriaan A. ;
Anker, Stefan D. ;
Pitt, Bertram ;
Pieske, Burkert ;
Filippatos, Gerasimos ;
Greene, Stephen J. ;
Gheorghiade, Mihai .
NATURE REVIEWS CARDIOLOGY, 2017, 14 (04) :238-250
[19]   Results of a Multicenter, Randomized, Double-Masked, Placebo-Controlled Clinical Study of the Efficacy and Safety of Visomitin Eye Drops in Patients with Dry Eye Syndrome [J].
Brzheskiy, Vladimir V. ;
Efimova, Elena L. ;
Vorontsova, Tatiana N. ;
Alekseev, Vladimir N. ;
Gusarevich, Olga G. ;
Shaidurova, Ksenia N. ;
Ryabtseva, Alla A. ;
Andryukhina, Olga M. ;
Kamenskikh, Tatiana G. ;
Sumarokova, Elena S. ;
Miljudin, Eugeny S. ;
Egorov, Eugeny A. ;
Lebedev, Oleg I. ;
Surov, Alexander V. ;
Korol, Andrii R. ;
Nasinnyk, Illia O. ;
Bezditko, Pavel A. ;
Muzhychuk, Olena P. ;
Vygodin, Vladimir A. ;
Yani, Elena V. ;
Savchenko, Alla Y. ;
Karger, Elena M. ;
Fedorkin, Oleg N. ;
Mironov, Alexander N. ;
Ostapenko, Victoria ;
Popeko, Natalia A. ;
Skulachev, Vladimir P. ;
Skulachev, Maxim V. .
ADVANCES IN THERAPY, 2015, 32 (12) :1263-1279
[20]   SYNTHESIS AND CHARACTERIZATION OF THIOBUTYLTRIPHENYLPHOSPHONIUM BROMIDE, A NOVEL THIOL REAGENT TARGETED TO THE MITOCHONDRIAL MATRIX [J].
BURNS, RJ ;
SMITH, RAJ ;
MURPHY, MP .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1995, 322 (01) :60-68