中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (6): 2523-2530.doi: 10.4103/NRR.NRR-D-24-01367

• 原著:退行性病与再生 • 上一篇    下一篇

成熟神经元低水平表达 c-Myc：维持神经元功能并防止神经退行性变

  

  • 出版日期:2026-06-15 发布日期:2026-04-18
  • 基金资助:

    国家自然科学基金项目（No. 81671263）

    安徽省教育厅科研创新团队项目（No. 2023AH010072）

    安徽省自然科学基金项目（No. 2208085MH221）

    安徽省教育厅国家重点科研项目(No.KJ2021A0851)

Low-level expression of Cmyc in mature neurons: Maintaining neuronal function and preventing neurodegeneration

Qi Dong1, #, Yanxia Ding1, #, Yingxin Zhou1, #, Xu Zhao1, Lei Hu1, *, Zhaohuan Zhang2, *, Xiaohui Xu1, 3, *   

  1. 1School of Preclinical Medicine, Wannan Medical College, Wuhu, Anhui Province, China; 
    2Department of Laboratory Medicine, Changzheng Hospital, Naval Medical University, Shanghai, China; 
    3Anhui Province Key Laboratory of Basic Research and Transformation of Age-related Diseases, Wannan Medical College, Wuhu, Anhui Province, China
  • Online:2026-06-15 Published:2026-04-18
  • Contact: Xiaohui Xu, PhD, MD, xhxu@wnmc.edu.cn; Zhaohuan Zhang, PhD, MD, zhaohuanpost2016@163.com; Lei Hu, PhD, huleiup@wnmc.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81671263 (to XX); Scientific Research and Innovation Team, Education Department of Anhui Province, China, No. 2023AH010072 (to XX); the Natural Science Foundation of Anhui Province, No. 2208085MH221 (to XX); The Key Projects for National Science Research of Education Department of Anhui Province, No. KJ2021A0851 (to YD).

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摘要： c-Myc作为经典的原癌蛋白，在成熟神经元中表达水平极低，传统观点认为c-Myc在这些细胞中并无功能。然而，最新研究表明，c-Myc在维持成熟多巴胺能神经元健康和功能方面可能起着至关重要的作用。此实验重新评估了Cmyc在多巴胺能神经元中的作用及其在帕金森病中的意义。以条件性敲除技术特异性地敲除了小鼠黑质神经元中的c-Myc基因。结果发现，c-Myc缺失导致小鼠在行为测试中表现出显著异常，包括在开放场测试中出现偏向左转的现象，表现出帕金森病样的运动障碍。高通量测序分析显示，c-Myc缺失后，Klotho等神经保护因子的表达显著下降，而与衰老相关的炎症标志物表达上调。研究还发现缺乏c-Myc的多巴胺能神经元出现衰老表型，并伴随氧化应激和神经炎症的增加。这些结果说明，低水平表达的c-Myc是维持Klotho正常表达抑制衰老和炎症因子的上调，从而保持多巴胺能神经元的年轻状态的关键。维持c-Myc和Klotho的正常表达水平，不仅对于预防帕金森病等年龄相关性神经退行性疾病至关重要，而且为该领域的治疗策略开发提供了新的研究方向。


https://orcid.org/0000-0001-7608-4114 (Xiaohui Xu); https://orcid.org/0000-0001-6882-9761 (Zhaohuan Zhang); https://orcid.org/0000-0002-1477-4096 (Lei Hu)

关键词: 衰老, c-Myc, 多巴胺能神经元, Klotho, 神经变性, 硝化α-突触核蛋白, 帕金森病

Abstract: Cmyc, a proto-oncogene, is expressed at extremely low levels in mature neurons and is traditionally thought to have no function in these cells. However, recent studies suggest that Cmyc may play a crucial role in maintaining the health and function of mature dopaminergic neurons. This study assessed the role of Cmyc in dopaminergic neurons and its significance in Parkinson’s disease. We used a conditional knockout approach to specifically delete Cmyc in substantia nigra dopaminergic neurons of adult mice. Our findings showed that Cmyc deletion led to progressive neuron loss, Parkinson’s disease-like symptoms, downregulation of Klotho, and upregulation of senescence-associated inflammatory factors, along with enhanced oxidative stress and nitrated alpha-synuclein accumulation, ultimately causing neuronal death. In vitro experiments confirmed increased senescence in C-MYC knockout cells, which was partially reversible by KLOTHO overexpression. We conclude that low-level Cmyc expression is essential for maintaining the health of mature dopaminergic neurons and preventing neurodegeneration, and suggest the c-Myc/Klotho axis as a potential therapeutic target for age-related neurodegenerative diseases, including Parkinson’s disease. Our study introduces a novel mouse model for Parkinson’s disease that replicates a condition associated with normal aging, offering a valuable tool for future research into disease mechanisms and therapeutic strategies.

Key words: aging, c-Myc, dopaminergic neurons, Klotho, neurodegeneration, nitrated alpha-synuclein, Parkinson’s disease