Oxidative stress, mitochondrial and proteostasis malfunction in adrenoleukodystrophy: A paradigm for axonal degeneration

Published on Nov 1, 2015in Free Radical Biology and Medicine5.66
· DOI :10.1016/j.freeradbiomed.2015.05.041
Stéphane Fourcade16
Estimated H-index: 16
Isidre Ferrer74
Estimated H-index: 74
Aurora Pujol35
Estimated H-index: 35
Abstract Peroxisomal and mitochondrial malfunction, which are highly intertwined through redox regulation, in combination with defective proteostasis, are hallmarks of the most prevalent multifactorial neurodegenerative diseases—including Alzheimer’s (AD) and Parkinson’s disease (PD)—and of the aging process, and are also found in inherited conditions. Here we review the interplay between oxidative stress and axonal degeneration, taking as groundwork recent findings on pathomechanisms of the peroxisomal neurometabolic disease adrenoleukodystrophy (X-ALD). We explore the impact of chronic redox imbalance caused by the excess of very long-chain fatty acids (VLCFA) on mitochondrial respiration and biogenesis, and discuss how this impairs protein quality control mechanisms essential for neural cell survival, such as the proteasome and autophagy systems. As consequence, prime molecular targets in the pathogenetic cascade emerge, such as the SIRT1/PGC-1α axis of mitochondrial biogenesis, and the inhibitor of autophagy mTOR. Thus, we propose that mitochondria-targeted antioxidants; mitochondrial biogenesis boosters such as the antidiabetic pioglitazone and the SIRT1 ligand resveratrol; and the autophagy activator temsirolimus, a derivative of the mTOR inhibitor rapamycin, hold promise as disease-modifying therapies for X-ALD.
  • References (168)
  • Citations (25)
#1Tomohiro Nakamura (Sanford-Burnham Institute for Medical Research)H-Index: 26
#2Olga Prikhodko (UCSD: University of California, San Diego)H-Index: 2
Last.Stuart A. Lipton (UCSD: University of California, San Diego)H-Index: 123
view all 10 authors...
65 CitationsSource
#1Laia Morató (University of Barcelona)H-Index: 5
#2Manuel Ruiz (University of Barcelona)H-Index: 13
Last.Aurora PujolH-Index: 35
view all 15 authors...
12 CitationsSource
#1Timothy Nacarelli (Drexel University)H-Index: 6
#2Ashley Azar (Drexel University)H-Index: 4
Last.Christian Sell (Drexel University)H-Index: 17
view all 3 authors...
29 CitationsSource
#1Yi Gong (Harvard University)H-Index: 3
#2Dakai Mu (Harvard University)H-Index: 9
Last.Florian Eichler (Harvard University)H-Index: 27
view all 9 authors...
25 CitationsSource
#1Nicol Kruska (Otto-von-Guericke University Magdeburg)H-Index: 4
#2Peter Schönfeld (Otto-von-Guericke University Magdeburg)H-Index: 27
Last.Georg Reiser (Otto-von-Guericke University Magdeburg)H-Index: 46
view all 4 authors...
20 CitationsSource
#1Mauhamad Baarine (MUSC: Medical University of South Carolina)H-Index: 5
#2Craig Beeson (MUSC: Medical University of South Carolina)H-Index: 34
Last.Inderjit Singh (MUSC: Medical University of South Carolina)H-Index: 61
view all 4 authors...
19 CitationsSource
#1Vincenzo Salpietro (UNIME: University of Messina)H-Index: 15
#2Rahul PhadkeH-Index: 19
Last.Maria KinaliH-Index: 34
view all 11 authors...
28 CitationsSource
#1Björn M. van GeelH-Index: 10
#2Bwee Tien Poll-The (UvA: University of Amsterdam)H-Index: 43
Last.Marc Engelen (UvA: University of Amsterdam)H-Index: 17
view all 6 authors...
23 CitationsSource
#1Nathalie LaunayH-Index: 7
#2Carmen AguadoH-Index: 16
Last.Aurora PujolH-Index: 35
view all 11 authors...
16 CitationsSource
#1Annelies Peeters (Katholieke Universiteit Leuven)H-Index: 12
#2Abhijit Babaji Shinde (Katholieke Universiteit Leuven)H-Index: 3
Last.Myriam Baes (Katholieke Universiteit Leuven)H-Index: 37
view all 13 authors...
38 CitationsSource
Cited By25
#1Simiao Qiao (CPU: China Pharmaceutical University)H-Index: 5
#2Rui Liu (CPU: China Pharmaceutical University)H-Index: 1
Last.Yue Dai (CPU: China Pharmaceutical University)H-Index: 22
view all 9 authors...
#1Maria Y. Pakharukova (NSU: Novosibirsk State University)H-Index: 6
#2Oxana G. Zaparina (RAS: Russian Academy of Sciences)H-Index: 1
Last.Viatcheslav A. Mordvinov (RAS: Russian Academy of Sciences)H-Index: 16
view all 4 authors...
#1Howard Friel (Northampton Community College)H-Index: 1
#1F. Tran Mau-Them (French Institute of Health and Medical Research)H-Index: 1
#2Laurent Guibaud (UCBL: Claude Bernard University Lyon 1)H-Index: 23
Last.Antonio Vitobello (French Institute of Health and Medical Research)H-Index: 4
view all 38 authors...
5 CitationsSource
#1Sumit Parikh (Cleveland Clinic)H-Index: 18
#2Amel Karaa (Harvard University)H-Index: 17
Last.Shamima Rahman (GOSH: Great Ormond Street Hospital)H-Index: 25
view all 25 authors...
#1Tommaso Schirinzi (University of Rome Tor Vergata)H-Index: 10
#2Gessica Vasco (Boston Children's Hospital)H-Index: 5
Last.Marco Cappa (Boston Children's Hospital)H-Index: 25
view all 12 authors...
3 CitationsSource
5 CitationsSource
#1Catherine A. Lee (UMN: University of Minnesota)H-Index: 8
#2Hannah S. Seo (UMN: University of Minnesota)H-Index: 1
Last.Samira M. Azarin (UMN: University of Minnesota)H-Index: 16
view all 6 authors...
5 CitationsSource
#1Desirèe Padilha Marchetti (UFRGS: Universidade Federal do Rio Grande do Sul)H-Index: 8
#2Luiza SteffensH-Index: 3
Last.Carmen Regla Vargas (UFRGS: Universidade Federal do Rio Grande do Sul)H-Index: 28
view all 13 authors...
View next paperEarly oxidative damage underlying neurodegeneration in X-adrenoleukodystrophy.