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Androgen-Dependent Neurodegeneration by Polyglutamine-Expanded Human Androgen Receptor in Drosophila
- Source :
- Neuron. 35:855-864
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- Spinal and bulbar muscular atrophy (SBMA) is an X-linked, adult-onset, neurodegenerative disorder affecting only males and is caused by expanded polyglutamine (polyQ) stretches in the N-terminal A/B domain of human androgen receptor (hAR). Although no overt phenotype was detected in adult fly eye photoreceptor neurons expressing mutant hAR (polyQ 52), ingestion of androgen or its known antagonists caused marked neurodegeneration with nuclear localization and structural alteration of the hAR mutant. Ligand-independent toxicity was detected with a truncated polyQ-expanded A/B domain alone, which was attenuated with cytosolic trapping by coexpression of the unliganded hAR E/F ligand binding domain. Thus, our findings suggest that the full binding of androgen to the polyQ-expanded hAR mutants leads to structural alteration with nuclear translocation that eventually results in the onset of SBMA in male patients.
- Subjects :
- medicine.medical_specialty
medicine.drug_class
Neuroscience(all)
Mutant
Biology
Animals, Genetically Modified
Muscular Atrophy, Spinal
Internal medicine
medicine
Animals
Humans
Receptor
Binding Sites
General Neuroscience
Neurodegeneration
Neurodegenerative Diseases
medicine.disease
Androgen
Phenotype
Cell biology
Androgen receptor
Spinal and bulbar muscular atrophy
Endocrinology
Receptors, Androgen
COS Cells
Gene Targeting
Drosophila
Photoreceptor Cells, Invertebrate
Peptides
Nuclear localization sequence
Subjects
Details
- ISSN :
- 08966273
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Neuron
- Accession number :
- edsair.doi.dedup.....867709af528207a6f91093751fcb4ee3