Department of Cell Biology, Section of Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, Groningen, The Netherlands.
Eur J Neurosci. 2010 Sep;32(5):760-70. doi: 10.1111/j.1460-9568.2010.07352.x. Epub 2010 Aug 19.
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.
在多聚谷氨酰胺疾病中，扩展的 CAG 重复序列的长度与疾病发病年龄呈强烈的负相关，但发病年龄的变化高达 50%是由其他额外因素决定的。在这里，我们研究了热休克蛋白 (HSP) 的表达变化是否与脊髓小脑共济失调 (SCA)3 患者发病年龄的差异有关。为此，我们分析了来自患者和健康对照的成纤维细胞中 HSPA1A（HSP70）、HSPA8（HSC70）、DNAJB（HSP40）和 HSPB1（HSP27）的蛋白表达水平。SCA3 患者的成纤维细胞中 HSPB1 水平显著上调，但与发病年龄无关。仅对于 DNAJB 家族成员的表达，发现与 CAG 重复扩展长度无关的发病年龄相关。这表明 DNAJB 成员可能是发病年龄变化的贡献者，并强调了 DNAJB 蛋白作为治疗靶点的可能用途。
