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MYC在神经退行性疾病和神经元修复中的隐匿作用。

Obscure Involvement of MYC in Neurodegenerative Diseases and Neuronal Repair.

作者信息

Marinkovic Tatjana, Marinkovic Dragan

机构信息

Western Serbia Academy of Applied Sciences, Uzice, Serbia.

Faculty of Special Education and Rehabilitation, University of Belgrade, Visokog Stevana 2, 11000, Belgrade, Serbia.

出版信息

Mol Neurobiol. 2021 Aug;58(8):4169-4177. doi: 10.1007/s12035-021-02406-w. Epub 2021 May 5.

DOI:10.1007/s12035-021-02406-w
PMID:33954904
Abstract

MYC is well known as a potent oncogene involved in regulating cell cycle and metabolism. Augmented MYC expression leads to cell cycle dysregulation, intense cell proliferation, and carcinogenesis. Surprisingly, its increased expression in neurons does not induce their proliferation, but leads to neuronal cell death and consequent development of a neurodegenerative phenotype. Interestingly, while cancer and neurodegenerative diseases such as Alzheimer's disease are placed at the opposite sides of cell division spectrum, both start with cell cycle dysregulation and stimulation of proliferation. It seems that MYC action directed toward neuron cell proliferation and neural tissue repair collides with evolutional loss of regenerative capacity of CNS neurons in order to strengthen synaptic structure, to protect our cognitive abilities and therefore character. Accordingly, there are abundant mechanisms that block its expression and action specifically in the brain. Moreover, while MYC expression in brain neurons during neurodegenerative processes is related to their death, there are obvious evidences that MYC action after physical injury is beneficial in case of peripheral nerve recovery. MYC might be a useful tool to repair brain cells upon development of neurodegenerative disease or CNS trauma, including stroke and traumatic brain and spinal cord injury, as even imperfect axonal growth and regeneration strategies will likely be of profound benefit. Understanding complex control of MYC action in the brain might have important therapeutic significance, but also it may contribute to the comprehension of development of neurodegenerative diseases.

摘要

MYC作为一种强大的癌基因,参与调节细胞周期和新陈代谢,广为人知。MYC表达增强会导致细胞周期失调、细胞过度增殖和致癌作用。令人惊讶的是,其在神经元中表达增加并不会诱导神经元增殖,反而会导致神经元细胞死亡,并进而引发神经退行性表型的发展。有趣的是,虽然癌症和神经退行性疾病(如阿尔茨海默病)处于细胞分裂谱的两端,但两者均始于细胞周期失调和增殖刺激。似乎MYC针对神经元细胞增殖和神经组织修复的作用,与中枢神经系统神经元为强化突触结构、保护我们的认知能力乃至性格特征而在进化过程中丧失的再生能力相冲突。因此,存在大量机制可特异性地阻断其在大脑中的表达和作用。此外,虽然神经退行性过程中脑神经元中的MYC表达与神经元死亡有关,但有明显证据表明,身体受伤后MYC的作用对外周神经恢复有益。在神经退行性疾病或中枢神经系统创伤(包括中风以及创伤性脑损伤和脊髓损伤)发生后,MYC可能是修复脑细胞的有用工具,因为即使是不完善的轴突生长和再生策略也可能会带来深远益处。了解大脑中MYC作用的复杂调控可能具有重要的治疗意义,同时也可能有助于理解神经退行性疾病的发展。

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