181 Citations (Scopus)

Abstract

Polyglutamine diseases are a family of neurodegenerative conditions that each derive from a CAG triplet repeat expansion in a specific gene. This produces a pathogenic protein that contains a critically expanded tract of glutamines. These prototypical protein misfolding disorders include Huntington disease, spinobulbar muscular atrophy, dentatorubral-pallidoluysian atrophy and several spinocerebellar ataxias. This article reviews the emerging concepts in pathogenesis and therapy. Key ideas include the role of proteolytic cleavage, the importance of conformational change in the pathogenic proteins, the role of protein aggregation and the importance of transcriptional and metabolic disturbances. The relative role of functional perturbation in a target protein induced by a polyglutamine expansion is also discussed. Therapeutic strategies include counteracting cellular perturbations and direct targeting of polyglutamine protein expression, cleavage or conformation.

Original languageEnglish (US)
JournalHuman Molecular Genetics
Volume16
Issue numberR2
DOIs
StatePublished - Oct 15 2007

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Proteins
Proteostasis Deficiencies
Progressive Myoclonic Epilepsy
Atrophic Muscular Disorders
Spinocerebellar Ataxias
Trinucleotide Repeats
Huntington Disease
Protein Transport
Therapeutics
Glutamine
polyglutamine
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Polyglutamine diseases : Emerging concepts in pathogenesis and therapy. / Shao, Jieya; Diamond, Marc I.

In: Human Molecular Genetics, Vol. 16, No. R2, 15.10.2007.

Research output: Contribution to journalArticle

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