Levels of DNAJB family members (HSP40) correlate with disease onset in patients with spinocerebellar ataxia type 3.
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.
Zijlstra
M P
MP
Department of Cell Biology, Section of Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, Groningen, The Netherlands.
Rujano
M A
MA
Van Waarde
M A
MA
Vis
E
E
Brunt
E R
ER
Kampinga
H H
HH
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000067699:Ataxin-3; D018929:Cell Culture Techniques; D002460:Cell Line; D002461:Cell Line, Transformed; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion; D015854:Up-Regulation
D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3