TY - JOUR
T1 - Potential therapeutic targets in polyglutamine-mediated diseases
AU - Katsuno, Masahisa
AU - Watanabe, Hirohisa
AU - Yamamoto, Masahiko
AU - Sobue, Gen
N1 - Funding Information:
This work was supported by KAKENHI from MEXT/JSPS, Japan (grant numbers 22110005, 26293206, 26670440, and 26670439); grants from Health Labor Sciences Research Grants, MHLW, Japan; CREST, JST; and a grant from the Daiichi Sankyo Foundation of Life Science. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Polyglutamine diseases are a group of inherited neurodegenerative disorders that are caused by an abnormal expansion of a trinucleotide CAG repeat, which encodes a polyglutamine tract in the protein-coding region of the respective disease genes. To date, nine polyglutamine diseases are known, including Huntington's disease, spinal and bulbar muscular atrophy, dentatorubral-pallidoluysian atrophy and six forms of spinocerebellar ataxia. These diseases share a salient molecular pathophysiology including the aggregation of the mutant protein followed by the disruption of cellular functions such as transcriptional regulation and axonal transport. The intraneuronal accumulation of mutant protein and resulting cellular dysfunction are the essential targets for the development of disease-modifying therapies, some of which have shown beneficial effects in animal models. In this review, the current status of and perspectives on therapy development for polyglutamine diseases will be discussed.
AB - Polyglutamine diseases are a group of inherited neurodegenerative disorders that are caused by an abnormal expansion of a trinucleotide CAG repeat, which encodes a polyglutamine tract in the protein-coding region of the respective disease genes. To date, nine polyglutamine diseases are known, including Huntington's disease, spinal and bulbar muscular atrophy, dentatorubral-pallidoluysian atrophy and six forms of spinocerebellar ataxia. These diseases share a salient molecular pathophysiology including the aggregation of the mutant protein followed by the disruption of cellular functions such as transcriptional regulation and axonal transport. The intraneuronal accumulation of mutant protein and resulting cellular dysfunction are the essential targets for the development of disease-modifying therapies, some of which have shown beneficial effects in animal models. In this review, the current status of and perspectives on therapy development for polyglutamine diseases will be discussed.
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U2 - 10.1586/14737175.2014.956727
DO - 10.1586/14737175.2014.956727
M3 - Review article
C2 - 25190502
AN - SCOPUS:84907918433
VL - 14
SP - 1215
EP - 1228
JO - Expert Review of Neurotherapeutics
JF - Expert Review of Neurotherapeutics
SN - 1473-7175
IS - 10
ER -