丙酮酸激酶2,一种能量代谢相关酶,可能在视网膜变性中具有神经保护功能。

IF 3.9 4区 医学 Q2 NEUROSCIENCES ASN NEURO Pub Date : 2023-01-01 DOI:10.1177/17590914231151534
Jiaming Zhou, Per Ekström
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引用次数: 0

摘要

色素性视网膜炎(RP)是一种导致视力损害的遗传性疾病,但目前还没有通用的和不依赖突变的治疗策略。然而,人们普遍认为cGMP系统,包括cGMP及其相互作用物cGMP依赖性蛋白激酶(PKG),在视网膜变性过程中起着至关重要的作用。我们之前已经确定了RP背景下cgmp - pkg依赖基因的列表,在本研究中,我们进一步验证了其中一个基因,即丙酮酸激酶2 (PKM2),并研究了PKM2在RP过程中对光感受器健康的潜在作用。借助器官型视网膜外植体培养,我们通过添加TEPP-46 (PKM2激活剂)对两种不同RP小鼠模型(rd2和rd10)的PKM2活性进行药理学处理,发现PKM2的激活可以缓解rd10小鼠模型中光受体死亡的进程。我们还注意到PKM2及其靶标之一葡萄糖转运蛋白-1 (Glut1)的表达随变性状态而改变。这些观察结果为PKM2可能作为RP新的潜在分子靶点提供了支持证据。
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Pyruvate Kinase 2, an Energy Metabolism Related Enzyme, May Have a Neuroprotective Function in Retinal Degeneration.

Retinitis pigmentosa (RP) is an inherited disorder that results in vision impairment but general and mutation-independent therapeutic strategies are not available. However, it is widely regarded that the cGMP system, including cGMP and its interactor cGMP-dependent protein kinase (PKG), acts as a crucial effector during retinal degeneration. We have previously identified a list of cGMP-PKG-dependent genes in the context of RP, and in this study, we further validated one of these, namely pyruvate kinase 2 (PKM2), and investigated the potential role of PKM2 for the photoreceptors' well-being during RP. With the aid of organotypic retinal explant cultures, we pharmacologically manipulated the PKM2 activities in two different RP mouse models (rd2 and rd10) via the addition of TEPP-46 (a PKM2 activator) and found that activation of PKM2 alleviates the progress of photoreceptor death in the rd10 mouse model. We also noted that the expression of both PKM2 and one of its targets, glucose transporter-1 (Glut1), showed alterations depending on the degeneration state. The observations provide supportive evidence that PKM2 may serve as a novel potential molecular target in RP.

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来源期刊
ASN NEURO
ASN NEURO NEUROSCIENCES-
CiteScore
7.70
自引率
4.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: ASN NEURO is an open access, peer-reviewed journal uniquely positioned to provide investigators with the most recent advances across the breadth of the cellular and molecular neurosciences. The official journal of the American Society for Neurochemistry, ASN NEURO is dedicated to the promotion, support, and facilitation of communication among cellular and molecular neuroscientists of all specializations.
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