Format

Send to

Choose Destination
Brain Res Bull. 2001 Oct-Nov 1;56(3-4):353-62.

Analysis of heat shock transcription factor for suppression of polyglutamine toxicity.

Author information

1
Dibit, San Raffaele Scientific Institute, Milano, Italy.

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.

PMID:
11719272
DOI:
10.1016/s0361-9230(01)00602-5
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center