Polyglutamine tract expansion of the androgen receptor in a motoneuronal model of spinal and bulbar muscular atrophy

Piccioni, Federica; Simeoni, Silvia; Andriola, I.; Armatura, Elena; Bassanini, Stefania; Pozzi, P.; Poletti, Angelo

doi:10.1016/s0361-9230(01)00652-9

Cited by 32 publications

(19 citation statements)

References 63 publications

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“…The relationship between an abnormally long CAG repeat in the exon 1 of the AR gene and the development of SBMA was the first observation to suggest that the polyglutamine tract might play a critical role in AR function [72,73] (Fig. 1).…”

Section: Effects Of Expanded Cag Repeats In the Ar Genementioning

confidence: 99%

Androgens and androgen receptors in breast cancer

Díaz-Chico

Rodrìguez

González

et al. 2007

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Effects Of Expanded Cag Repeats In the Ar Genementioning

confidence: 99%

Androgens and androgen receptors in breast cancer

Díaz-Chico

Rodrìguez

González

et al. 2007

The Journal of Steroid Biochemistry and Molecular Biology

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“…Mouse C3H10T1/2 fibroblast cells express endogenous AR, and DHT inhibits their differentiation into adipocytes and promotes the expression of MyoD and myosin heavy chain type II (MHC2; Compston 2001. In addition to satellite cells, AR is expressed in mature myofibers (Saartok et al 1984, Sar et al 1990) in several types of motoneurons (Lumbroso et al 1996, Piccioni et al 2001, and in intramuscular fibroblasts (Monks et al 2004), and thus could influence growth and function through activation in these cells. Finally, androgens regulate systemic levels of IGF1, GH, and thyroid hormone, and may oppose the actions of glucocorticoids, any of which could contribute to the effects of androgen on muscle (Link et al 1986, Hickson et al 1990, Banu et al 2002, Ferrando et al 2002.…”

Section: Introductionmentioning

confidence: 99%

Androgen-mediated improvement of body composition and muscle function involves a novel early transcriptional program including IGF1, mechano growth factor, and induction of β-catenin

Gentile¹,

Nantermet²,

Vogel³

et al. 2009

Journal of Molecular Endocrinology

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Androgens promote anabolism in the musculoskeletal system while generally repressing adiposity, leading to lean body composition. Circulating androgens decline with age, contributing to frailty, osteoporosis, and obesity; however, the mechanisms by which androgens modulate body composition are largely unknown. Here, we demonstrate that aged castrated rats develop increased fat mass, reduced muscle mass and strength, and lower bone mass. Treatment with testosterone or 5a-dihydrotestosterone (DHT) reverses the effects on muscle and adipose tissues while only aromatizable testosterone increased bone mass. During the first week, DHT transiently increased soleus muscle nuclear density and induced expression of IGF1 and its splice variant mechano growth factor (MGF) without early regulation of the myogenic factors MyoD, myogenin, monocyte nuclear factor, or myostatin. A genome-wide microarray screen was also performed to identify potential pro-myogenic genes that respond to androgen receptor activation in vivo within 24 h. Of 24 000 genes examined, 70 candidate genes were identified whose functions suggest initiation of remodeling and regeneration, including the type II muscle genes for myosin heavy chain type II and parvalbumin and the chemokine monocyte chemoattractant protein-1. Interestingly, Axin and Axin2, negative regulators of b-catenin, were repressed, indicating modulation of the b-catenin pathway. DHT increased total levels of b-catenin protein, which accumulated in nuclei in vivo. Likewise, treatment of C2C12 myoblasts with both IGF1Ea and MGF C-terminal peptide increased nuclear b-catenin in vitro. Thus, we propose that androgenic anabolism involves early downregulation of Axin and induction of IGF1, leading to nuclear accumulation of b-catenin, a pro-myogenic, anti-adipogenic stem cell regulatory factor.

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“…In particular, phosphorylation at serine 175/176 via c-Jun N-terminal kinase-3 (referred to as JNK3) (13)(14)(15)(16)(17) is associated with Huntington disease and spinal and bulbar muscular atrophy. JNK3 activation is known to be up-regulated in the presence of pathogenic huntingtin or androgen receptor (15,16).…”

mentioning

confidence: 99%

Motor Domain Phosphorylation Modulates Kinesin-1 Transport

DeBerg

Blehm

Sheung

et al. 2013

Journal of Biological Chemistry

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Background: Kinesin-1 motor domain phosphorylation has been linked to impaired transport in axons. Results: A mechanism by which phosphorylation could affect transport is proposed. Conclusion: Phosphorylation decreases the stall force of kinesin and stabilizes autoinhibition. Significance: Kinesin phosphorylation could be used to fine tune the direction of cargo transport and contribute to pathology in neurodegenerative disease.

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Polyglutamine tract expansion of the androgen receptor in a motoneuronal model of spinal and bulbar muscular atrophy

Cited by 32 publications

References 63 publications

Androgens and androgen receptors in breast cancer

Androgens and androgen receptors in breast cancer

Androgen-mediated improvement of body composition and muscle function involves a novel early transcriptional program including IGF1, mechano growth factor, and induction of β-catenin

Motor Domain Phosphorylation Modulates Kinesin-1 Transport

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