ArticleBrain : a journal of neurology2013
Pioglitazone halts axonal degeneration in a mouse model of X-linked adrenoleukodystrophy.
Article in Brain : a journal of neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 78 citations in OpenAlex.
- PPARγ Signaling in the Central Nervous System: A Review of the Implications in Synaptic Plasticity, Neuroinflammatory and Neoplastic Processes.Neurochemical research · 2026Review
- Alginate-encapsulated enzymes mitigate deoxynivalenol-induced hepatic mitochondrial dysfunction and glycolithocholic acid accumulation in piglets.Journal of animal science and biotechnology · 2026Article
- Nervonic acid and the long arc of therapeutic hope in X-linked adrenoleukodystrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Pioglitazone Ameliorates Mitochondrial Oxidative Stress and Inflammation via AMPK-Dependent Inhibition of Mitochondrial Fission in Leigh Syndrome.Cell proliferation · 2026Article
- Pioglitazone as a Possible Treatment forBiomolecules · 2024Review
- Development of PPARγ Agonists for the Treatment of Neuroinflammatory and Neurodegenerative Diseases: Leriglitazone as a Promising Candidate.International journal of molecular sciences · 2023Review
- Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing.Frontiers in cell and developmental biology · 2023Review
- Activating cannabinoid receptor 2 preserves axonal health through GSK-3β/NRF2 axis in adrenoleukodystrophy.Acta neuropathologica · 2022Article
- Beneficial Effects of the Direct AMP-Kinase Activator PXL770 in In Vitro and In Vivo Models of X-Linked Adrenoleukodystrophy.The Journal of pharmacology and experimental therapeutics · 2022Article
- Therapeutic potential of deuterium-stabilized (R)-pioglitazone-PXL065-for X-linked adrenoleukodystrophy.Journal of inherited metabolic disease · 2022Article
- The clinical spectrum of X-linked adrenoleukodystrophy: from Addison's-only in men to middle-age neurologic manifestations in women.Hormones (Athens, Greece) · 2022Review
- The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy.Frontiers in nutrition · 2022Review
- ABCD1 and X-linked adrenoleukodystrophy: A disease with a markedly variable phenotype showing conserved neurobiology in animal models.Journal of neuroscience research · 2021Review
- Drug discovery for X-linked adrenoleukodystrophy: An unbiased screen for compounds that lower very long-chain fatty acids.Journal of cellular biochemistry · 2021Article
- Peroxisomal ABC Transporters: An Update.International journal of molecular sciences · 2021Review
- The Advanced Lipoxidation End-Product Malondialdehyde-Lysine in Aging and Longevity.Antioxidants (Basel, Switzerland) · 2020Review
- High-dose biotin restores redox balance, energy and lipid homeostasis, and axonal health in a model of adrenoleukodystrophy.Brain pathology (Zurich, Switzerland) · 2020Article
- The Changing Face of Adrenoleukodystrophy.Endocrine reviews · 2020Review
- Enhanced axonal response of mitochondria to demyelination offers neuroprotection: implications for multiple sclerosis.Acta neuropathologica · 2020Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
X-linked adrenoleukodystrophy is a neurometabolic disorder caused by inactivation of the peroxisomal ABCD1 transporter of very long-chain fatty acids. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative stress and bioenergetic failure play major roles in the pathogenesis of X-linked adrenoleukodystrophy. In this study, we aimed to evaluate whether mitochondrial biogenesis is affected in X-linked adrenoleukodystrophy. We demonstrated that Abcd1 null mice show reduced mitochondrial DNA concomitant with downregulation of mitochondrial biogenesis pathway driven by PGC-1α/PPARγ and reduced expression of mitochondrial proteins cytochrome c, NDUFB8 and VDAC. Moreover, we show that the oral administration of pioglitazone, an agonist of PPARγ, restored mitochondrial content and expression of master regulators of biogenesis, neutralized oxidative damage to proteins and DNA, and reversed bioenergetic failure in terms of ATP levels, NAD+/NADH ratios, pyruvate kinase and glutathione reductase activities. Most importantly, the treatment halted locomotor disability and axonal damage in X-linked adrenoleukodystrophy mice. These results lend support to the use of pioglitazone in clinical trials with patients with adrenomyeloneuropathy and reveal novel molecular mechanisms of action of pioglitazone in neurodegeneration. Future studies should address the effects of this anti-diabetic drug on other axonopathies in which oxidative stress and mitochondrial dysfunction are contributing factors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.