α-突触核蛋白诱导的不稳定BMAL1 mRNA导致帕金森病的昼夜节律中断。

IF 2.9 3区医学 Q2 NEUROSCIENCES

Neurotoxicity Research Pub Date : 2023-04-01 DOI:10.1007/s12640-022-00633-0

Jun-Yi Liu, Jian Xue, Fen Wang, Ya-Li Wang, Wan-Li Dong

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引用次数: 0

摘要

昼夜节律障碍是帕金森病(PD)常见的非运动症状。加重α-突触核蛋白(SNCA)对昼夜节律紊乱的潜在影响尚不清楚。本研究采用过表达SNCAA53T的转基因小鼠(SNCAA53T小鼠)和野生型(WT)仔鼠。能量代谢笼试验显示，SNCAA53T小鼠与WT小鼠在24小时活动模式上存在差异。与同龄的幼崽相比，SNCAA53T小鼠的脑和肌肉arnt样1 (BMAL1)下调。BMAL1在过表达SNCA的PC12细胞中下调。SNCA过表达后，BMAL1蛋白的降解保持不变，但其mRNA水平下降。miRNA (miR)-155通过SNCA的过表达而上调，BMAL1的下调通过转染miR-155抑制剂被部分逆转。我们的研究结果表明，SNCA的过表达通过miR-155降低BMAL1 mRNA的稳定性，诱导生物节律中断并下调BMAL1的表达。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

α-Synuclein-Induced Destabilized BMAL1 mRNA Leads to Circadian Rhythm Disruption in Parkinson's Disease.

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α-Synuclein-Induced Destabilized BMAL1 mRNA Leads to Circadian Rhythm Disruption in Parkinson's Disease.

Circadian dysfunction is a common non-motor symptom in Parkinson's disease (PD). The potential influence of aggravated α-synuclein (SNCA) on circadian disruption remains unclear. SNCA^A53T-overexpressing transgenic mice (SNCA^A53T mice) and wild-type (WT) littermates were used in this study. The energy metabolism cage test showed differences in 24-h activity pattern between SNCA^A53T and WT mice. When compared with the age-matched littermates, brain and muscle ARNT-like 1 (BMAL1) was downregulated in SNCA^A53T mice. BMAL1 was downregulated in PC12 cells overexpressing SNCA. Degradation of BMAL1 protein remained unchanged after overexpression of SNCA, while its mRNA level decreased. miRNA (miR)-155 was upregulated by overexpression of SNCA, and downregulation of BMAL1 was partially reversed by transfection with miR-155 inhibitor. Our findings demonstrated that overexpression of SNCA induced biorhythm disruption and downregulated BMAL1 expression through decreasing stability of BMAL1 mRNA via miR-155.

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来源期刊

Neurotoxicity Research 医学-神经科学

CiteScore

7.70

自引率

5.40%

发文量

164

审稿时长

6-12 weeks

期刊介绍： Neurotoxicity Research is an international, interdisciplinary broad-based journal for reporting both basic and clinical research on classical neurotoxicity effects and mechanisms associated with neurodegeneration, necrosis, neuronal apoptosis, nerve regeneration, neurotrophin mechanisms, and topics related to these themes. Published papers have focused on: NEURODEGENERATION and INJURY Neuropathologies Neuronal apoptosis Neuronal necrosis Neural death processes (anatomical, histochemical, neurochemical) Neurodegenerative Disorders Neural Effects of Substances of Abuse NERVE REGENERATION and RESPONSES TO INJURY Neural Adaptations Neurotrophin mechanisms and actions NEURO(CYTO)TOXICITY PROCESSES and NEUROPROTECTION Excitatory amino acids Neurotoxins, endogenous and synthetic Reactive oxygen (nitrogen) species Neuroprotection by endogenous and exogenous agents Papers on related themes are welcome.