PuSH - Publication Server of Helmholtz Zentrum München

Dong, G.* ; Gross, K.* ; Qiao, F.* ; Ferguson, J.* ; Callegari, E.A.* ; Rezvani, K.* ; Zhang, D.* ; Gloeckner, C.J. ; Ueffing, M. ; Wang, H.*

Calretinin interacts with huntingtin and reduces mutant huntingtin-caused cytotoxicity.

J. Neurochem. 123, 437-446 (2012)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expansion of CAG trinucleotide repeats encoding for polyglutamine (polyQ) in the huntingtin (Htt) gene. Despite considerable effort, the mechanisms underlying the toxicity of the mutated Htt protein remains largely uncertain. To identify novel therapeutic targets, we recently employed the approach of tandem affinity purification and discovered that calretinin (Cr), a member of the EF-hand family of calcium-binding proteins, is preferentially associated with mHtt, although it also interacts with wild-type Htt. These observations were supported by coimmunoprecipitation and by colocalization of Cr with mHtt in neuronal cultures. Over- expression of Cr reduced mHtt-caused cytotoxicity in both non-neuronal and neuronal cell models of HD, whereas knockdown of Cr expression in the cells enhanced mHtt-caused neuronal cell death. In addition, over-expression of Cr was also associated with reduction of intracellular free calcium and activation of Akt. These results suggest that Cr may be a potential therapeutic target for treatment of HD.
Altmetric
Additional Metrics?
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0022-3042
e-ISSN 1471-4159
Quellenangaben Volume: 123, Issue: 3, Pages: 437-446 Article Number: , Supplement: ,
Publisher Wiley
Reviewing status Peer reviewed