Huntington's disease: Pathomechanism and therapeutic perspectives

G. Gárdián, L. Vécsei

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Huntington's disease is an autosomal dominantly inherited progressive neurodegenerative disorder. The mutant gene has been localised to chromosome 4p16.3. The gene product huntingtin is widely distributed in both neurones and extraneuronal tissues. The mutation in Huntington's disease involves the expansion of a trinucleotide (CAG) repeat encoding glutamine. The etiology of Huntington's disease is yet unknown but increasing evidence suggests important role of altered gene transcription, mitochondrial dysfunction and excitotoxicity. The expanded polyglutamine stretch leads to a conformational change and abnormal protein-protein interactions. Mutant huntingtin can bind to transcription factors, resulting in reduced levels of acetylated histones. One consequence of this appears to be a decreased expression of genes which may play critical roles in neuronal survival. To date, a number of palliative therapies have been demonstrated to be effective in reducing the motor features, and particularly the chorea, but no treatment is at hand for the other symptoms of Huntington's disease. However, these treatments produce very limited symptomatic benefit. In the absence of disease-modifying treatment, the other avenue is the neural transplantation. However, recent advances in understanding have furnished new hope that a therapeutic strategy may one day be possible.

Original languageEnglish
Pages (from-to)1485-1494
Number of pages10
JournalJournal of Neural Transmission
Volume111
Issue number10-11
DOIs
Publication statusPublished - Oct 2004

Fingerprint

Huntington Disease
Trinucleotide Repeats
Chorea
Mitochondrial Genes
Therapeutics
Glutamine
Palliative Care
Neurodegenerative Diseases
Histones
Genes
Proteins
Transcription Factors
Hand
Chromosomes
Transplantation
Gene Expression
Neurons
Mutation

Keywords

  • Altered gene expression
  • CAG trinucleotide repeat expansion
  • Excitotoxicity
  • Huntington's disease
  • Mitochondrial dysfunction
  • Neural transplantation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Huntington's disease : Pathomechanism and therapeutic perspectives. / Gárdián, G.; Vécsei, L.

In: Journal of Neural Transmission, Vol. 111, No. 10-11, 10.2004, p. 1485-1494.

Research output: Contribution to journalArticle

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