Emerging concepts in the therapy of mitochondrial disease

被引：86

作者：

Viscomi, Carlo ^{[1
,2
]}

Bottani, Emanuela ^{[2
]}

Zeviani, Massimo ^{[1
,2
]}

机构：

[1] Fdn Carlo Besta Inst Neurol IRCCS, Unit Mol Neurogenet, I-20133 Milan, Italy

[2] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS | 2015年 / 1847卷 / 6-7期

关键词：

Mitochondrion; Experimental therapy; Oxidative phosphorilation; Mitochondrial respiratory chain; Mitochondrial disease; Animal model; TRANSFER-RNA SYNTHETASE; CORRECTS BIOCHEMICAL DERANGEMENTS; OPTIMIZED ALLOTOPIC EXPRESSION; HEREDITARY OPTIC NEUROPATHY; RESPIRATORY-CHAIN DEFECTS; IN-VITRO SUPPLEMENTATION; LARGE-SCALE DELETIONS; GENE-THERAPY; COMPLEX-I; ALTERNATIVE OXIDASE;

D O I：

10.1016/j.bbabio.2015.03.001

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：

Mitochondrial disorders are an important group of genetic conditions characterized by impaired oxidative phosphorylation. Mitochondrial disorders come with an impressive variability of symptoms, organ involvement, and clinical course, which considerably impact the quality of life and quite often shorten the lifespan expectancy. Although the last 20 years have witnessed an exponential increase in understanding the genetic and biochemical mechanisms leading to disease, this has not resulted in the development of effective therapeutic approaches, amenable of improving clinical course and outcome of these conditions to any significant extent. Therapeutic options for mitochondrial diseases still remain focused on supportive interventions aimed at relieving complications. However, new therapeutic strategies have recently been emerging, some of which have shown potential efficacy at the pre-clinical level. This review will present the state of the art on experimental therapy for mitochondrial disorders. Crown Copyright (C) 2015 Published by Elsevier B.V.

引用

页码：544 / 557

页数：14

共 165 条

[1] Ketogenic diet slows down mitochondrial myopathy progression in mice [J].

Ahola-Erkkila, Sofia ;

Carroll, Christopher J. ;

Peltola-Mjosund, Katja ;

Tulkki, Valtteri ;

Mattila, Ismo ;

Seppanen-Laakso, Tuulikki ;

Oresic, Matej ;

Tyynismaa, Henna ;

Suomalainen, Anu .

HUMAN MOLECULAR GENETICS, 2010, 19 (10) :1974-1984

[2] OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28 [J].

Alexander, C ;

Votruba, M ;

Pesch, UEA ;

Thiselton, DL ;

Mayer, S ;

Moore, A ;

Rodriguez, M ;

Kellner, U ;

Leo-Kottler, B ;

Auburger, G ;

Bhattacharya, SS ;

Wissinger, B .

NATURE GENETICS, 2000, 26 (02) :211-215

[3]

Alexeyev MF, 2008, GENE THER, V15, P516, DOI [10.1038/gt.2008.11, 10.1038/sj.gt.2008.11]

[4] Modulating mtDNA heteroplasmy by mitochondria-targeted restriction endonucleases in a 'differential multiple cleavage-site' model [J].

Bacman, S. R. ;

Williams, S. L. ;

Hernandez, D. ;

Moraes, C. T. .

GENE THERAPY, 2007, 14 (18) :1309-1318

[5] Manipulation of mtDNA heteroplasmy in all striated muscles of newborn mice by AAV9-mediated delivery of a mitochondria-targeted restriction endonuclease [J].

Bacman, S. R. ;

Williams, S. L. ;

Duan, D. ;

Moraes, C. T. .

GENE THERAPY, 2012, 19 (11) :1101-1106

[6] Organ-specific shifts in mtDNA heteroplasmy following systemic delivery of a mitochondria-targeted restriction endonuclease [J].

Bacman, S. R. ;

Williams, S. L. ;

Garcia, S. ;

Moraes, C. T. .

GENE THERAPY, 2010, 17 (06) :713-720

[7] Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs [J].

Bacman, Sandra R. ;

Williams, Sion L. ;

Pinto, Milena ;

Peralta, Susana ;

Moraes, Carlos T. .

NATURE MEDICINE, 2013, 19 (09) :1111-1113

[8] Activation of peroxisome proliferator-activated receptor pathway stimulates the mitochondrial respiratory chain and can correct deficiencies in patients' cells lacking its components [J].

Bastin, Jean ;

Aubey, Flore ;

Rotig, Agnes ;

Munnich, Arnold ;

Djouadi, Fatima .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (04) :1433-1441

[9] Rapid directional shift of mitochondrial DNA heteroplasmy in animal tissues by a mitochondrially targeted restriction endonuclease [J].

Bayona-Bafaluy, MP ;

Blits, B ;

Battersby, BJ ;

Shoubridge, EA ;

Moraes, CT .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (40) :14392-14397

[10] Quantifying small molecule phenotypic effects using mitochondrial morpho-functional fingerprinting and machine learning [J].

Blanchet, Lionel ;

Smeitink, Jan A. M. ;

van Emst-de Vries, Sjenet E. ;

Vogels, Caroline ;

Pellegrini, Mina ;

Jonckheere, An I. ;

Rodenburg, Richard J. T. ;

Buydens, Lutgarde M. C. ;

Beyrath, Julien ;

Willems, Peter H. G. M. ;

Koopman, Werner J. H. .

SCIENTIFIC REPORTS, 2015, 5 :1-7

← 1 2 3 4 5 6 7 8 9 10 →