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计算机分析揭示了阿尔茨海默病患者小脑离子跨膜转运体的调节作用。

In Silico Analysis Reveals the Modulation of Ion Transmembrane Transporters in the Cerebellum of Alzheimer's Disease Patients.

机构信息

IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.

出版信息

Int J Mol Sci. 2023 Sep 10;24(18):13924. doi: 10.3390/ijms241813924.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder. AD hallmarks are extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles in the brain. It is interesting to notice that Aβ plaques appear in the cerebellum only in late stages of the disease, and then it was hypothesized that it can be resistant to specific neurodegenerative mechanisms. However, the role of cerebellum in AD pathogenesis is not clear yet. In this study, we performed an in silico analysis to evaluate the transcriptional profile of cerebellum in AD patients and non-AD subjects in order to deepen the knowledge on its role in AD. The analysis evidenced that only the molecular function (MF) "active ion transmembrane transporter activity" was overrepresented. Regarding the 21 differentially expressed genes included in this MF, some of them may be involved in the ion dyshomeostasis reported in AD, while others assumed, in the cerebellum, an opposite regulation compared to those reported in other brain regions in AD patients. They might be associated to a protective phenotype, that may explain the initial resistance of cerebellum to neurodegeneration in AD. Of note, this MF was not overrepresented in prefrontal cortex and visual cortex indicating that it is a peculiarity of the cerebellum.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病。AD 的特征是脑内细胞外淀粉样β(Aβ)斑块和细胞内神经原纤维缠结。有趣的是,Aβ斑块仅在疾病的晚期出现在小脑,然后有人假设它可以抵抗特定的神经退行性机制。然而,小脑在 AD 发病机制中的作用尚不清楚。在这项研究中,我们进行了一项计算机分析,以评估 AD 患者和非 AD 受试者小脑的转录谱,以加深对其在 AD 中的作用的了解。分析表明,只有分子功能(MF)“主动离子跨膜转运体活性”过表达。对于包含在这个 MF 中的 21 个差异表达基因,其中一些可能与 AD 中报道的离子失衡有关,而另一些则假设在小脑与 AD 患者其他脑区报道的相反。它们可能与保护表型有关,这可以解释小脑在 AD 中对神经退行性变的初始抵抗。值得注意的是,这个 MF 在额皮质和视觉皮质中没有过表达,这表明它是小脑的一个特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b01/10530854/c47ecbfb9970/ijms-24-13924-g001.jpg

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