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DNAJB6 在人脑神经元和少突胶质细胞中表达。

DNAJB6 is expressed in neurons and oligodendrocytes of the human brain.

机构信息

Centre for Neuroscience and Stereology, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, Denmark.

Department of Science and Environment, Roskilde University, Roskilde, Denmark.

出版信息

Glia. 2024 Dec;72(12):2313-2326. doi: 10.1002/glia.24615. Epub 2024 Sep 3.

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.

摘要

DNAJB6 是体内和体外α-突触核蛋白聚集的抑制剂。DNAJB6 在大脑中强烈表达,其总蛋白表达在神经退行性疾病如帕金森病(PD)和多系统萎缩(MSA)等情况下发生改变。这两种疾病的特征分别是神经元和少突胶质细胞中聚集的α-突触核蛋白的积累。为了进一步探讨这一点,我们使用死后正常人类脑组织来研究 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广泛表达。值得注意的是,我们首次证明 DNAJB6 存在于近一半(41%-53%)的少突胶质细胞群体中和大多数(68%-80%)的神经元中。然而,DNAJB6 仅在其他细胞类型如星形胶质细胞和小胶质细胞中稀疏存在。鉴于寡突胶质细胞中α-突触核蛋白的聚集是 MSA 的标志,我们研究了 MSA 大脑与对照大脑中 DNAJB6 的存在情况。我们发现 MSA 大脑中 DNAJB6 存在的少突胶质细胞百分比与对照大脑相比没有显著差异。总之,我们的结果揭示了 DNAJB6 蛋白在人类大脑各个区域的表达,并且 DNAJB6 几乎仅存在于神经元和少突胶质细胞中。由于先前的研究表明 PD 和 MSA 大脑中 DNAJB6 的水平相对于对照大脑发生改变,因此 DNAJB6 可能是药物开发的一个有趣目标。

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