ArticleHuman molecular genetics2015
Synergic prodegradative activity of Bicalutamide and trehalose on the mutant androgen receptor responsible for spinal and bulbar muscular atrophy.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- 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
- Targeting androgen receptor stability and degradation: approaches for developing a therapy for spinal and bulbar muscular atrophy.Cell communication and signaling : CCS · 2025Review
- Bicalutamide and Trehalose Ameliorate Spinal and Bulbar Muscular Atrophy Pathology in Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Mechanistic Insights and Potential Therapeutic Approaches in PolyQ Diseases via Autophagy.Biomedicines · 2023Review
- The role of autophagy-lysosomal pathway in motor neuron diseases.Biochemical Society transactions · 2022Review
- The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases.International journal of molecular sciences · 2022Review
- Exploring the Role of Posttranslational Modifications in Spinal and Bulbar Muscular Atrophy.Frontiers in molecular neuroscience · 2022Review
- Cell-Clearing Systems Bridging Repeat Expansion Proteotoxicity and Neuromuscular Junction Alterations in ALS and SBMA.International journal of molecular sciences · 2020Review
- Enhanced Clearance of Neurotoxic Misfolded Proteins by the Natural Compound Berberine and Its Derivatives.International journal of molecular sciences · 2020Article
- The Role of Sex and Sex Hormones in Neurodegenerative Diseases.Endocrine reviews · 2020Review
- A Crucial Role for the Protein Quality Control System in Motor Neuron Diseases.Frontiers in aging neuroscience · 2020Article
- Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration.Autophagy · 2019Article
- Autophagic and Proteasomal Mediated Removal of Mutant Androgen Receptor in Muscle Models of Spinal and Bulbar Muscular Atrophy.Frontiers in endocrinology · 2019Article
- The Regulation of the Small Heat Shock Protein B8 in Misfolding Protein Diseases Causing Motoneuronal and Muscle Cell Death.Frontiers in neuroscience · 2019Review
- Autophagy induction by trehalose: Molecular mechanisms and therapeutic impacts.Journal of cellular physiology · 2018Review
- Dual role of autophagy on docetaxel-sensitivity in prostate cancer cells.Cell death & disease · 2018Article
- Tdp-25 Routing to Autophagy and Proteasome Ameliorates its Aggregation in Amyotrophic Lateral Sclerosis Target Cells.Scientific reports · 2018Article
- Trehalose protects against oxidative stress by regulating the Keap1-Nrf2 and autophagy pathways.Redox biology · 2018Article
- The small heat shock protein B8 (HSPB8) efficiently removes aggregating species of dipeptides produced in C9ORF72-related neurodegenerative diseases.Cell stress & chaperones · 2018Article
- Inhibition of retrograde transport modulates misfolded protein accumulation and clearance in motoneuron diseases.Autophagy · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
Abstract
Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease due to a CAG triplet-repeat expansion in the androgen receptor (AR) gene, which is translated into an elongated polyglutamine (polyQ) tract in AR protein (ARpolyQ). ARpolyQ toxicity is activated by the AR ligand testosterone (or dihydrotestosterone), and the polyQ triggers ARpolyQ misfolding and aggregation in spinal cord motoneurons and muscle cells. In motoneurons, testosterone triggers nuclear toxicity by inducing AR nuclear translocation. Thus, (i) prevention of ARpolyQ nuclear localization, combined with (ii) an increased ARpolyQ cytoplasmic clearance, should reduce its detrimental activity. Using the antiandrogen Bicalutamide (Casodex(®)), which slows down AR activation and nuclear translocation, and the disaccharide trehalose, an autophagy activator, we found that, in motoneurons, the two compounds together reduced ARpolyQ insoluble forms with higher efficiency than that obtained with single treatments. The ARpolyQ clearance was mediated by trehalose-induced autophagy combined with the longer cytoplasmic retention of ARpolyQ bound to Bicalutamide. This allows an increased recognition of misfolded species by the autophagic system prior to their migration into the nucleus. Interestingly, the combinatory use of trehalose and Bicalutamide was also efficient in the removal of insoluble species of AR with a very long polyQ (Q112) tract, which typically aggregates into the cell nuclei. Collectively, these data suggest that the combinatory use of Bicalutamide and trehalose is a novel approach to facilitate ARpolyQ clearance that has to be tested in other cell types target of SBMA (i.e. muscle cells) and in vivo in animal models of SBMA.
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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.