ArticleHuman molecular genetics2016
A small-molecule Nrf1 and Nrf2 activator mitigates polyglutamine toxicity in spinal and bulbar muscular atrophy.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 75 citations in OpenAlex.
- Safety and Efficacy of Nanocurcumin as Add-On Therapy to Riluzole in Patients With Amyotrophic Lateral Sclerosis: A Pilot Randomized Clinical Trial.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Trial
- Coordinated control of proteasome subunit gene expression promotes stress resistance, proteostasis, and longevity.GeroScience · 2026Article
- The alternative androgen receptor isoform A mitigates toxicity of polyglutamine-elongated mutant androgen receptor in spinal and bulbar muscular atrophy.Journal of advanced research · 2026Article
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.PLoS genetics · 2026Article
- Unveiling the effect of curcumin on ion channels of SBMA motoneuron-derived cells and human IPSC-derived neurons: initial electrophysiological findings.European biophysics journal : EBJ · 2026Article
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.bioRxiv : the preprint server for biology · 2025Article
- Identification of a novel and high-affinity cyclic peptide targeting Keap1 for inflammation treatment by a combined virtual screening strategy.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Targeting androgen receptor stability and degradation: approaches for developing a therapy for spinal and bulbar muscular atrophy.Cell communication and signaling : CCS · 2025Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Activation of the 26S Proteasome to Reduce Proteotoxic Stress and Improve the Efficacy of PROTACs.ACS pharmacology & translational science · 2025Review
- Erucin, a Natural Isothiocyanate, Prevents Polyglutamine-Induced Toxicity inInternational journal of molecular sciences · 2024Article
- Mutations in nucleotide metabolism genes bypass proteasome defects in png-1/NGLY1-deficient Caenorhabditis elegans.PLoS biology · 2024Article
- The Role of NRF2 in Trinucleotide Repeat Expansion Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo.Experimental neurology · 2024Article
- Natural products reverse cancer multidrug resistance.Frontiers in pharmacology · 2024Review
- A phenotypically robust model of spinal and bulbar muscular atrophy in Drosophila.Journal of neuroscience research · 2024Article
- Role of NFE2L1 in the Regulation of Proteostasis: Implications for Aging and Neurodegenerative Diseases.Biology · 2023Review
- Article
- Therapeutic Potential of Natural Compounds in Neurodegenerative Diseases: Insights from Clinical Trials.Pharmaceutics · 2023Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Spinal and bulbar muscular atrophy (SBMA, also known as Kennedy's disease) is one of nine neurodegenerative disorders that are caused by expansion of polyglutamine-encoding CAG repeats. Intracellular accumulation of abnormal proteins in these diseases, a pathological hallmark, is associated with defects in protein homeostasis. Enhancement of the cellular proteostasis capacity with small molecules has therefore emerged as a promising approach to treatment. Here, we characterize a novel curcumin analog, ASC-JM17, as an activator of central pathways controlling protein folding, degradation and oxidative stress resistance. ASC-JM17 acts on Nrf1, Nrf2 and Hsf1 to increase the expression of proteasome subunits, antioxidant enzymes and molecular chaperones. We show that ASC-JM17 ameliorates toxicity of the mutant androgen receptor (AR) responsible for SBMA in cell, fly and mouse models. Knockdown of the Drosophila Nrf1 and Nrf2 ortholog cap 'n' collar isoform-C, but not Hsf1, blocks the protective effect of ASC-JM17 on mutant AR-induced eye degeneration in flies. Our observations indicate that activation of the Nrf1/Nrf2 pathway is a viable option for pharmacological intervention in SBMA and potentially other polyglutamine diseases.
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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.