Soluble androgen receptor oligomers underlie pathology in a mouse model of spinobulbar muscular atrophy

Mei Li, Erica S. Chevalier-Larsen, Diane E. Merry, Marc I. Diamond

Research output: Contribution to journalArticle

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Abstract

In polyglutamine diseases such as X-linked spinobulbar muscular atrophy (SBMA), it is unknown whether the toxic form of the protein is an insoluble or soluble aggregate or a monomer. We have addressed this question by studying a full-length androgen receptor (AR) mouse model of SBMA. We used biochemistry and atomic force microscopy to immunopurify oligomers soluble after ultracentrifugation that are comprised of a single ∼50-kDa N-terminal polyglutamine-containing AR fragment. AR oligomers appeared several weeks prior to symptom onset, were distinct and temporally dissociated from intranuclear inclusions, and disappeared rapidly after castration, which halts disease. This is the first demonstration of soluble AR oligomers in vivo and suggests that they underlie neurodegeneration in SBMA.

Original languageEnglish (US)
Pages (from-to)3157-3164
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number5
DOIs
StatePublished - Jan 2 2007

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Atrophic Muscular Disorders
Androgen Receptors
Pathology
Oligomers
Intranuclear Inclusion Bodies
Atomic Force Microscopy
Poisons
Ultracentrifugation
Castration
Biochemistry
Atomic force microscopy
Demonstrations
Monomers
Proteins
polyglutamine

ASJC Scopus subject areas

  • Biochemistry

Cite this

Soluble androgen receptor oligomers underlie pathology in a mouse model of spinobulbar muscular atrophy. / Li, Mei; Chevalier-Larsen, Erica S.; Merry, Diane E.; Diamond, Marc I.

In: Journal of Biological Chemistry, Vol. 282, No. 5, 02.01.2007, p. 3157-3164.

Research output: Contribution to journalArticle

Li, Mei ; Chevalier-Larsen, Erica S. ; Merry, Diane E. ; Diamond, Marc I. / Soluble androgen receptor oligomers underlie pathology in a mouse model of spinobulbar muscular atrophy. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 5. pp. 3157-3164.
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