Levels of DNAJB family members (HSP40) correlate with disease onset in patients with spinocerebellar ataxia type 3

M. P. Zijlstra, M. A. Rujano, M. A. Van Waarde, E. Vis, E. R. Brunt, H. H. Kampinga*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    30 Citations (Scopus)

    Abstract

    In polyglutamine disorders, the length of the expanded CAG repeat shows a strong inverse correlation with the age at disease onset, yet up to 50% of the variation in age of onset is determined by other additional factors. Here, we investigated whether variations in the expression of heat shock proteins (HSP) are related to differences in the age of onset in patients with spinocerebellar ataxia (SCA)3. Hereto, we analysed the protein expression levels of HSPA1A (HSP70), HSPA8 (HSC70), DNAJB (HSP40) and HSPB1 (HSP27) in fibroblasts from patients and healthy controls. HSPB1 levels were significantly upregulated in fibroblasts from patients with SCA3, but without relation to age of onset. Exclusively for expression of DNAJB family members, a correlation was found with the age of onset independent of the length of the CAG repeat expansion. This indicates that DNAJB members might be contributors to the variation in age of onset and underlines the possible use of DNAJB proteins as therapeutic targets.

    Original languageEnglish
    Pages (from-to)760-770
    Number of pages11
    JournalEuropean Journal of Neuroscience
    Volume32
    Issue number5
    DOIs
    Publication statusPublished - Sep-2010

    Keywords

    • age at onset
    • CAG repeat
    • fibroblasts
    • heat shock proteins
    • SCA3
    • MACHADO-JOSEPH-DISEASE
    • ALPHA-B-CRYSTALLIN
    • HEAT-SHOCK-PROTEIN
    • POLYGLUTAMINE DISEASE
    • MOLECULAR CHAPERONES
    • HUNTINGTONS-DISEASE
    • CEREBELLAR ATAXIAS
    • GENDER EQUALITY
    • MUTANT ATAXIN-3
    • CAG REPEAT

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