Webbläsaren som du använder stöds inte av denna webbplats. Alla versioner av Internet Explorer stöds inte längre, av oss eller Microsoft (läs mer här: * https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Var god och använd en modern webbläsare för att ta del av denna webbplats, som t.ex. nyaste versioner av Edge, Chrome, Firefox eller Safari osv.

Overexpression of heat shock protein 70 in R6/2 Huntington's disease mice has only modest effects on disease progression.

In English

Författare

  • Oskar Hansson
  • Jesper Nylandsted
  • Roger F Castilho
  • Marcel Leist
  • Marja Jäättelä
  • Patrik Brundin

Summary, in English

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 1 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.

Publiceringsår

2003

Språk

Engelska

Sidor

47-57

Publikation/Tidskrift/Serie

Brain Research

Volym

970

Issue

1-2

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Neurosciences

Nyckelord

  • Heat shock protein 70 (Hsp70)
  • Inclusion
  • Huntington’s disease
  • Chaperone
  • Transgenic
  • Mouse

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1872-6240