Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization

Akira Sawa, Gordon W. Wiegand, Jillian Cooper, Russell L. Margolis, Alan H. Sharp, Joseph F. Lawler, J. Timothy Greenamyre, Solomon H. Snyder, Christopher A. Ross

Research output: Contribution to journalArticlepeer-review

302 Scopus citations

Abstract

Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats coding for glutamine in the HD gene product huntingtin. Although HD symptoms reflect preferential neuronal death in specific brain regions, huntingtin is expressed in almost all tissues, so abnormalities outside the brain might be expected. Although involvement of nuclei and mitochondria in HD pathophysiology has been suggested, specific intracellular defects that might elicit cell death have been unclear. Mitochondria dysfunction is reported in HD brains; mitochondria are organelles that regulates apoptotic cell death. We now report that lymphoblasts derived from HD patients showed increased stress-induced apoptotic cell death associated with caspase-3 activation. When subjected to stress, HD lymphoblasts also manifested a considerable increase in mitochondrial depolarization correlated with increased glutamine repeats.

Original languageEnglish (US)
Pages (from-to)1194-1198
Number of pages5
JournalNature medicine
Volume5
Issue number10
DOIs
StatePublished - Oct 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization'. Together they form a unique fingerprint.

Cite this