FUS is not dysregulated by the spinal bulbar muscular atrophy androgen receptor polyglutamine repeat expansion

NEUROBIOLOGY OF AGING

卷:34

Article

Fratta, Pietro^1,2  Malik, Bilal^2,3  Gray, Anna^2,3  La Spada, Albert R.^4,5,6  Hanna, Michael G.²  Fisher, Elizabeth M. C.^1,2  Greensmith, Linda^2,3 

[1] UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England

[2] UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England

[3] UCL Inst Neurol, Sobell Dept, London WC1N 3BG, England

[4] Univ Calif San Diego, Dept Pediat, Dept Cellular & Mol Med, Div Genet, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[6] Rady Childrens Hosp, San Diego, CA USA

关键词: Amyotrophic lateral sclerosis;    Fused in sarcoma;    TLS;    Kennedy's Disease;    Motor neuron disease;    Spinal bulbar muscular atrophy;   

DOI  :  10.1016/j.neurobiolaging.2012.09.008

来源: Elsevier

【 摘 要 】

Spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis are two distinct forms of motor neuron disease with different genetic causes, pathology, and clinical course. However, both disorders are characterized by the progressive loss of lower motor neurons and by a similar protective response to growth factors in animal models, therefore raising the possibility of an overlap in the final pathogenic cascade. Mutations in the FUS gene and fused in sarcoma (FUS) protein pathology have now been identified in some amyotrophic lateral sclerosis cases, while a CAG expansion in the androgen receptor gene is known to cause SBMA. Recently, multiple lines of evidence have identified FUS as a major target of the androgen receptor, suggesting that FUS could be dysregulated in SBMA motor neurons. We have investigated this possibility by using a well-established mouse model of SBMA and our analysis of primary motor neuron cultures, spinal cords, and microdissected motor neurons show no evidence for FUS dysregulation. (C) 2013 Elsevier Inc. All rights reserved.

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