Yang Yana, Tao Yunlong
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, China.
Cell Prolif. 2025 Jun;58(6):e13807. doi: 10.1111/cpr.13807. Epub 2025 Jan 28.
Pathological changes in the locus coeruleus-norepinephrine (LC-NE) neurons, the major source of norepinephrine (NE, also known as noradrenaline) in the brain, are evident during the early stages of neurodegenerative diseases (ND). Research on both human and animal models have highlighted the therapeutic potential of targeting the LC-NE system to mitigate the progression of ND and alleviate associated psychiatric symptoms. However, the early and widespread degeneration of the LC-NE system presents a significant challenge for direct intervention in ND. Recent advances in regenerative cell therapy offer promising new strategies for ND treatment. The regeneration of LC-NE from pluripotent stem cells (PSCs) could significantly broaden the scope of LC-NE-based therapies for ND. In this review, we delve into the fundamental background and physiological functions of LC-NE. Additionally, we systematically examine the evidence and role of the LC-NE system in the neuropathology of ND and psychiatric diseases over recent years. Notably, we focus on the significance of PSCs-derived LC-NE and its potential impact on ND therapy. A deeper understanding and further investigation into the regeneration of LC-NE function could pave the way for practical and effective treatments for ND.
蓝斑去甲肾上腺素（LC-NE）神经元是大脑中去甲肾上腺素（NE，也称为去甲肾上腺素）的主要来源，其病理变化在神经退行性疾病（ND）的早期阶段就很明显。对人类和动物模型的研究都强调了靶向LC-NE系统以减轻ND进展和缓解相关精神症状的治疗潜力。然而，LC-NE系统早期广泛的退化对直接干预ND提出了重大挑战。再生细胞疗法的最新进展为ND治疗提供了有前景的新策略。从多能干细胞（PSC）再生LC-NE可以显著拓宽基于LC-NE的ND治疗范围。在这篇综述中，我们深入探讨了LC-NE的基本背景和生理功能。此外，我们系统地研究了近年来LC-NE系统在ND和精神疾病神经病理学中的证据和作用。值得注意的是，我们关注PSC衍生的LC-NE的意义及其对ND治疗的潜在影响。对LC-NE功能再生的更深入理解和进一步研究可为ND的实际有效治疗铺平道路。
