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通过干预趋化因子轴介导的神经细胞通讯来治疗帕金森病的功能单体装备微凝胶系统

Functional Monomers Equipped Microgel System for Managing Parkinson's Disease by Intervening Chemokine Axis-mediated Nerve Cell Communications.

作者信息

Jiang Lin, Zhang Xu, Wang Shun, Zhang Jiangkuan, Chen Junyang, Lu Jiachuan, Yao Liting, Jin Weiwei, Li Nan, Li Qing

机构信息

College of Life Sciences, China Jiliang University, Hangzhou, 310018, China.

Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, China.

出版信息

Adv Sci (Weinh). 2025 Feb;12(7):e2410070. doi: 10.1002/advs.202410070. Epub 2024 Dec 25.

Abstract

The complex pathology of Parkinson's disease (PD) requires comprehensive understanding and multi-pronged interventions for communication between nerve cells. Despite new developments in nanotechnology in the treatment of PD, in-depth exploration of their biological effects, in particular, the specific mechanisms of inflammation inhibition are lacking. Herein, using the stable cascade catalysis channel formed by polydopamine (PDA), imidazole groups, and Cu ions, a microgel system comprising functional monomers [superoxide dismutase (SOD) with double bonds, PDA, 2-methacryloyloxy ethyl phosphorylcholine (MPC), and Cu ions] is proposed for managing PD. The microgel can be efficiently delivered to the brain aided by MPC, after which a multi-level regulatory strategy targeting neurons and microglia can be initiated. The catalytic activity cascade elicited by SOD and Cu ions can regulate the anti-inflammatory phenotypic transformation of microglia by relieving oxidative stress. Meanwhile, the dopamine (DA) released from PDA can facilitate DA storage and neurogenesis, inhibiting CX3CL1 release and the CX3CR1 receptor on microglia and further regulating the CX3CL1/CX3CR1-NF-κB-NLRP3 signaling pathway in microglia to inhibit neuroinflammation. Therefore, the proposed microgel delivery system with functional monomers represents a promising therapeutic strategy for managing neuroinflammation and promoting neurogenesis in PD by intervening chemokine axis-mediated communication between neurons and microglia.

摘要

帕金森病(PD)复杂的病理学需要全面理解以及针对神经细胞间通讯的多管齐下的干预措施。尽管纳米技术在PD治疗方面有新进展,但对其生物学效应,尤其是炎症抑制的具体机制仍缺乏深入探索。在此,利用聚多巴胺(PDA)、咪唑基团和铜离子形成的稳定级联催化通道,提出了一种包含功能单体[具有双键的超氧化物歧化酶(SOD)、PDA、2-甲基丙烯酰氧乙基磷酰胆碱(MPC)和铜离子]的微凝胶系统来治疗PD。该微凝胶在MPC的辅助下可有效递送至大脑,之后可启动针对神经元和小胶质细胞的多层次调控策略。由SOD和铜离子引发的催化活性级联反应可通过减轻氧化应激来调节小胶质细胞的抗炎表型转化。同时,从PDA释放的多巴胺(DA)可促进DA储存和神经发生,抑制小胶质细胞上CX3CL1的释放和CX3CR1受体,并进一步调节小胶质细胞中的CX3CL1/CX3CR1-NF-κB-NLRP3信号通路以抑制神经炎症。因此,所提出的具有功能单体的微凝胶递送系统是一种有前景的治疗策略,可通过干预趋化因子轴介导的神经元与小胶质细胞间通讯来管理PD中的神经炎症并促进神经发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a814/11831437/8035c8b57ae6/ADVS-12-2410070-g003.jpg

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