ArticleScience translational medicine2012
PGC-1α rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 281 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
281 citing papers in PubMed, 1 synthesis or guideline pooled it, 427 citations in OpenAlex.
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- Glutathione Biology in Neurodegenerative and Metabolic Diseases: Molecular Mechanisms, Pathophysiological Roles, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- TFEB Antagonizes Cardiac Hypertrophy and Failure by Enhancing Lysosomal Capacity and Mitochondrial Function.Circulation research · 2026Article
- The Role of PGC-1α in Neurodegenerative Diseases: Molecular Mechanisms, Translational Challenges, and Therapeutic Potential.Molecular neurobiology · 2026Review
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Review
- TFEB degradation is regulated by an IKK/β-TrCP2 phosphorylation-ubiquitination cascade.Nature communications · 2026Article
- Identification of KHS-101 as a Transcription Factor EB Activator to Promote α-Synuclein Degradation.International journal of molecular sciences · 2026Article
- STUB1-mediated PGC-1α ubiquitination promotes postoperative cognitive dysfunction in aged mice via modulating autophagy-lysosome machinery.European journal of medical research · 2025Article
- Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Ubiquitination of TFEB increased intestinal permeability to aggravate metabolic dysfunction-associated steatohepatitis.Hepatology (Baltimore, Md.) · 2025Article
- ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions.Molecular biomedicine · 2025Review
- Impairment of lysosomal quality control in Huntington disease.Cell death & disease · 2025Article
- Autophagy and Cellular Senescence in Alzheimer's Disease: Key Drivers of Neurodegeneration.CNS neuroscience & therapeutics · 2025Review
- ER-induced PERK/TFEB cascade sequentially modulates mitochondrial dynamics during cranial suture expansion.Bone research · 2025Article
- TFEB-dependent autophagy-lysosomal pathway is required for NRF2-driven antioxidative action in obstructive sleep apnea-induced neuronal injury.Cellular signalling · 2025Article
- Antioxidant and Anti-Inflammatory Defenses in Huntington's Disease: Roles of NRF2 and PGC-1α, and Therapeutic Strategies.Life (Basel, Switzerland) · 2025Review
- From Molecular Therapies to Lysosomal Transplantation and Targeted Drug Strategies: Present Applications, Limitations, and Future Prospects of Lysosomal Medications.Biomolecules · 2025Review
221 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Huntington's disease (HD) is caused by CAG repeat expansions in the huntingtin (htt) gene, yielding proteins containing polyglutamine repeats that become misfolded and resist degradation. Previous studies demonstrated that mutant htt interferes with transcriptional programs coordinated by the peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α), a regulator of mitochondrial biogenesis and oxidative stress. We tested whether restoration of PGC-1α could ameliorate the symptoms of HD in a mouse model. We found that PGC-1α induction virtually eliminated htt protein aggregation and ameliorated HD neurodegeneration in part by attenuating oxidative stress. PGC-1α promoted htt turnover and the elimination of protein aggregates by activating transcription factor EB (TFEB), a master regulator of the autophagy-lysosome pathway. TFEB alone was capable of reducing htt aggregation and neurotoxicity, placing PGC-1α upstream of TFEB and identifying these two molecules as important therapeutic targets in HD and potentially other neurodegenerative disorders caused by protein misfolding.
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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.