論文

査読有り 国際誌
2020年10月

Disease mechanism, biomarker and therapeutics for spinal and bulbar muscular atrophy (SBMA).

Journal of neurology, neurosurgery, and psychiatry
  • Atsushi Hashizume
  • ,
  • Kenneth H Fischbeck
  • ,
  • Maria Pennuto
  • ,
  • Pietro Fratta
  • ,
  • Masahisa Katsuno

91
10
開始ページ
1085
終了ページ
1091
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1136/jnnp-2020-322949

Spinal and bulbar muscular atrophy (SBMA) is a hereditary neuromuscular disorder caused by CAG trinucleotide expansion in the gene encoding the androgen receptor (AR). In the central nervous system, lower motor neurons are selectively affected, whereas pathology of patients and animal models also indicates involvement of skeletal muscle including loss of fast-twitch type 2 fibres and increased slow-twitch type 1 fibres, together with a glycolytic-to-oxidative metabolic switch. Evaluation of muscle and fat using MRI, in addition to biochemical indices such as serum creatinine level, are promising biomarkers to track the disease progression. The serum level of creatinine starts to decrease before the onset of muscle weakness, followed by the emergence of hand tremor, a prodromal sign of the disease. Androgen-dependent nuclear accumulation of the polyglutamine-expanded AR is an essential step in the pathogenesis, providing therapeutic opportunities via hormonal manipulation and gene silencing with antisense oligonucleotides. Animal studies also suggest that hyperactivation of Src, alteration of autophagy and a mitochondrial deficit underlie the neuromuscular degeneration in SBMA and provide alternative therapeutic targets.

リンク情報
DOI
https://doi.org/10.1136/jnnp-2020-322949
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32934110

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