DNAJB6 is expressed in neurons and oligodendrocytes of the human brain

IF 5.4 2区 医学 Q1 NEUROSCIENCES Glia Pub Date : 2024-09-03 DOI:10.1002/glia.24615
Jónvá Hentze, Jonas Folke, Susana Aznar, Pia Nyeng, Tomasz Brudek, Christian Hansen
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Abstract

DNAJB6 is a suppressor of α-synuclein aggregation in vivo and in vitro. DNAJB6 is strongly expressed in the brain, and its overall protein expression is altered in neurodegenerative conditions such as Parkinson's Disease (PD) and Multiple System Atrophy (MSA). These two diseases are characterized by accumulation of aggregated α-synuclein in neurons and oligodendrocytes, respectively. To further explore this, we employed post-mortem normal human brain material to investigate the regional and cell type specific protein expression of DNAJB6. We found that the DNAJB6 protein is ubiquitously expressed across various regions of the brain. Notably, we demonstrate for the first time that DNAJB6 is present in nearly half (41%–53%) of the oligodendrocyte population and in the majority (68%–80%) of neurons. However, DNAJB6 was only sparsely present in other cell types such as astrocytes and microglia. Given that α-synuclein aggregation in oligodendrocytes is a hallmark of MSA, we investigated DNAJB6 presence in MSA brains compared to control brains. We found no significant difference in the percentage of oligodendrocytes where DNAJB6 was present in MSA brains relative to control brains. In conclusion, our results reveal an expression of the DNAJB6 protein across various regions of the human brain, and that DNAJB6 is almost exclusively present in neurons and oligodendrocytes. Since prior studies have shown that PD and MSA brains have altered levels of DNAJB6 relative to control brains, DNAJB6 may be an interesting target for drug development.

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DNAJB6 在人脑的神经元和少突胶质细胞中表达。
DNAJB6 是体内和体外α-突触核蛋白聚集的抑制因子。DNAJB6在大脑中的表达量很高,在帕金森病(PD)和多系统萎缩症(MSA)等神经退行性疾病中,DNAJB6的整体蛋白表达量会发生改变。这两种疾病的特征是α-突触核蛋白分别在神经元和少突胶质细胞中聚集。为了进一步探讨这一问题,我们利用死后正常人脑材料研究了 DNAJB6 的区域和细胞类型特异性蛋白表达。我们发现,DNAJB6 蛋白在大脑的各个区域都有普遍表达。值得注意的是,我们首次证明 DNAJB6 存在于近一半(41%-53%)的少突胶质细胞和大多数(68%-80%)的神经元中。然而,DNAJB6 只稀少地存在于其他细胞类型,如星形胶质细胞和小胶质细胞。鉴于少突胶质细胞中的α-突触核蛋白聚集是MSA的特征之一,我们对MSA大脑中DNAJB6的存在情况进行了调查,并与对照组大脑进行了比较。我们发现,与对照组大脑相比,MSA 大脑中 DNAJB6 存在的少突胶质细胞比例没有明显差异。总之,我们的研究结果揭示了 DNAJB6 蛋白在人脑各区域的表达情况,而且 DNAJB6 几乎只存在于神经元和少突胶质细胞中。由于先前的研究表明,相对于对照组大脑,帕金森病和多发性硬化症患者大脑中的 DNAJB6 水平发生了改变,因此 DNAJB6 可能是一个有趣的药物开发靶点。
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来源期刊
Glia
Glia 医学-神经科学
CiteScore
13.10
自引率
4.80%
发文量
162
审稿时长
3-8 weeks
期刊介绍: GLIA is a peer-reviewed journal, which publishes articles dealing with all aspects of glial structure and function. This includes all aspects of glial cell biology in health and disease.
期刊最新文献
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