Analysis of heat shock transcription factor for suppression of polyglutamine toxicity

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Individually over-expressed chaperones can interfere with cytotoxicity and aggregation of polyglutamine proteins in disease models. As chaperones cooperate, the analysis of suppression or reversal of polyglutamine pathology may require ways to up-regulate multiple chaperone coding genes. This condition might be achieved by exogenous expression of de-repressed forms of heat shock transcription factor 1 (HSF1), which mediates induction of several genes coding cytosolic and nuclear chaperones. Here we present the rationale behind this possible approach and the caveats, and employ a non-neuronal cell system to test whether Ataxin-1 aggregation can be modulated by de-repressed HSF1 mutants through augmented expression of chaperone coding genes. In our experiments, HSF1 mutants have induced heat shock protein 70 and Human DnaJ (HDJ)-1 to intermediate levels. Cells expressing such mutants also showed partial reduction of Ataxin-1 [31Q] aggregation. A consolidated positive outcome of these tests in cellular models would encourage experiments in transgenic mice and prospects for pharmacological modulation of HSF1 activity or delivery.

Original languageEnglish
Pages (from-to)353-362
Number of pages10
JournalBrain Research Bulletin
Volume56
Issue number3-4
DOIs
Publication statusPublished - Nov 1 2001

Fingerprint

Genes
HSP70 Heat-Shock Proteins
Transgenic Mice
Up-Regulation
Pharmacology
Pathology
polyglutamine
heat shock transcription factor
Proteins
Ataxin-1

Keywords

  • Chaperones
  • Cytotoxicity
  • HSF1
  • Polyglutamine proteins
  • Transcriptional regulation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Analysis of heat shock transcription factor for suppression of polyglutamine toxicity. / Rimoldi, Monica; Servadio, Antonio; Zimarino, Vincenzo.

In: Brain Research Bulletin, Vol. 56, No. 3-4, 01.11.2001, p. 353-362.

Research output: Contribution to journalArticle

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