A new pathway for neuroprotection against tau hyperphosphorylation via δ-opioid receptor initiated inhibition of CDK5 and AMPK signaling.

IF 4.1 2区医学 Q2 GERIATRICS & GERONTOLOGY

Frontiers in Aging Neuroscience Pub Date : 2025-06-24 eCollection Date: 2025-01-01 DOI:10.3389/fnagi.2025.1587219

Jiahui Li, Yuan Xu, Gianfranco Balboni, Ying Xia

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引用次数: 0

Abstract

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by decreased memory and cognitive impairment. Abnormal tau hyperphosphorylation ultimately forms neurofibrillary tangles, which is one of the most important pathological features of AD. Since we have previously shown that the δ-opioid receptor (DOR) is neuroprotective in the brain, we asked if DOR plays any role in the control of tauopathy.

Methods: In the PC12 cell model with okadaic acid-induced tau hyperphosphorylation, cell viability and cytotoxicity were evaluated by using CCK8 assay kit and lactate dehydrogenase cytotoxicity assay kit. The techniques of western blot and immunofluorescence were used to investigate the effect of DOR on tau hyperphosphorylation.

Results: We found that DOR activation inhibited okadaic acid-induced tau hyperphosphorylation in PC12 cells and attenuated the cell cycle reactivation and apoptosis. The DOR effect was blocked by Naltrindole, a DOR antagonist. Furthermore, the mechanistic studies showed that the DOR displayed its effect by reducing the expression of cyclin-dependent kinase (CDK) 5 and AMP-activated protein kinase (AMPK) in the model of tauopathy.

Discussion: Our novel findings suggest that DOR signaling may protect neurons from AD injury by inhibiting tau hyperphosphorylation.

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通过δ-阿片受体启动的CDK5和AMPK信号抑制抑制tau过度磷酸化的神经保护新途径。

简介：阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是记忆力下降和认知功能障碍。异常的tau过度磷酸化最终形成神经原纤维缠结，这是AD最重要的病理特征之一。由于我们之前已经证明δ-阿片受体（DOR）在大脑中具有神经保护作用，我们想知道DOR是否在控制牛头病中起任何作用。方法：采用CCK8检测试剂盒和乳酸脱氢酶细胞毒性检测试剂盒，对冈田酸诱导tau过磷酸化的PC12细胞模型进行细胞活力和细胞毒性检测。采用western blot和免疫荧光技术研究DOR对tau蛋白过度磷酸化的影响。结果：DOR激活抑制冈田酸诱导的PC12细胞tau过度磷酸化，并减弱细胞周期再激活和凋亡。DOR效应被一种DOR拮抗剂纳曲多阻断。此外，机制研究表明，DOR通过降低细胞周期蛋白依赖性激酶（CDK） 5和amp活化蛋白激酶（AMPK）在牛头病变模型中的表达来发挥其作用。讨论：我们的新发现表明DOR信号可能通过抑制tau过度磷酸化来保护神经元免受AD损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Aging Neuroscience GERIATRICS & GERONTOLOGY-NEUROSCIENCES

CiteScore

6.30

自引率

8.30%

发文量

1426

期刊介绍： Frontiers in Aging Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the mechanisms of Central Nervous System aging and age-related neural diseases. Specialty Chief Editor Thomas Wisniewski at the New York University School of Medicine is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.