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CDK1 在视网膜变性晚期的潜在作用

A Potential Role of Cyclic Dependent Kinase 1 (CDK1) in Late Stage of Retinal Degeneration.

机构信息

Ophthalmology, Department of Clinical Sciences Lund, Lund University, 223 62 Lund, Sweden.

出版信息

Cells. 2022 Jul 7;11(14):2143. doi: 10.3390/cells11142143.

DOI:10.3390/cells11142143
PMID:35883586
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9317054/
Abstract

Cyclin dependent kinase 1 (CDK1) has long been known to drive the cell cycle and to regulate the division and differentiation of cells. Apart from its role in mitosis regulation, it also exerts multiple functions as a protein kinase, including engagement in cell death, possibly via a cell cycle-independent mechanism. The latter is suggested, since CDK1 re-expression can be found in non-dividing and terminally differentiated neurons in several neurodegeneration models. However, the details of if and how CDK1 might be involved in the neurodegenerative condition, retinitis pigmentosa (RP), which displays progressive vision loss, are unclear. In the present study, we investigated CDK1 in degenerating RP photoreceptors of the RP model, including whether there is a link between this kinase and the cGMP-PKG system, which is regarded as a disease driver. With experiments performed using either in vivo retinal tissue or in vitro material, via organotypic retinal explants, our results showed that CDK1 appears in the photoreceptors at a late stage of their degeneration, and in such a position, it may be associated with the cGMP-PKG network.

摘要

周期蛋白依赖性激酶 1(CDK1)长期以来一直被认为可以驱动细胞周期,并调节细胞的分裂和分化。除了在有丝分裂调节中的作用外,它还作为一种蛋白激酶发挥多种功能,包括参与细胞死亡,可能通过非细胞周期依赖的机制。这一点是有依据的,因为在几种神经退行性模型中,在非分裂和终末分化的神经元中可以发现 CDK1 的重新表达。然而,CDK1 是否以及如何可能参与神经退行性疾病——色素性视网膜炎(RP),其表现为进行性视力丧失的具体细节尚不清楚。在本研究中,我们研究了 RP 模型中退化的 RP 光感受器中的 CDK1,包括这种激酶与被认为是疾病驱动因素的 cGMP-PKG 系统之间是否存在联系。通过使用体内视网膜组织或体外材料(通过器官型视网膜外植体)进行实验,我们的结果表明,CDK1 在光感受器退化的晚期出现,并且在这种位置,它可能与 cGMP-PKG 网络相关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5edd/9317054/93fac9bbb5b9/cells-11-02143-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5edd/9317054/46fd3d4ce750/cells-11-02143-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5edd/9317054/93fac9bbb5b9/cells-11-02143-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5edd/9317054/46fd3d4ce750/cells-11-02143-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5edd/9317054/93fac9bbb5b9/cells-11-02143-g002.jpg

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Exp Eye Res. 2021 Sep;210:108701. doi: 10.1016/j.exer.2021.108701. Epub 2021 Jul 10.
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Cellular mechanisms of hereditary photoreceptor degeneration - Focus on cGMP.
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Biol Reprod. 2019 Nov 21;101(5):878-881. doi: 10.1093/biolre/ioz143.
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Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration.环鸟苷酸类似物与药物递送系统的联合应用为遗传性视网膜退行性病变提供了功能保护。
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