Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/81540
Type: Artigo de periódico
Title: Overexpression of heat shock protein 70 in R6/2 Huntington's disease mice has only modest effects on disease progression
Author: Hansson, O
Nylandsted, J
Castilho, RF
Leist, M
Jaattela, M
Brundin, P
Abstract: Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of a polyglutamine tract in a protein called huntingtin. The inducible form of heat shock protein 70 (Hsp70) has been shown to reduce polyglutamine-induced toxicity. To investigate if overexpression of Hsp70 can affect disease progression in a mouse model of HD, we crossed R6/2 mice, expressing exon I of the HD gene with an expanded CAG repeat, with mice overexpressing Hsp70 (both types of transgenic mice were of the CBAxC57BL/6 strain). The resulting R6/2-Hsp70 transgenics exhibited 5- to 15-fold increases in Hsp70 expression in neocortical, hippocampal and basal ganglia regions. This correlated with a delayed loss of body weight compared to R6/2 mice. However, the number or size of nuclear inclusions, the loss of brain weight, reduction of striatal volume, reduction in size of striatal projection neurons, downregulation of DARPP-32, development of paw clasping phenotype and early death of the mice were not affected by Hsp70 overexpression. Interestingly, the polyglutamine protein affected the potential rescuing agent, because in older R6/2-Hsp70 mice a large proportion of the Hsp70 protein was sequestrated in nuclear inclusions. (C) 2002 Elsevier Science B.V. All rights reserved.
Subject: Huntington's disease
inclusion
heat shock protein 70 (Hsp70)
chaperone
transgenic
mouse
Country: Holanda
Editor: Elsevier Science Bv
Rights: fechado
Identifier DOI: 10.1016/S0006-8993(02)04275-0
Date Issue: 2003
Appears in Collections:Unicamp - Artigos e Outros Documentos

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