Gardenia-derived extracellular vesicles exert therapeutic effects on dopaminergic neuron apoptosis-mediated Parkinson’s disease

IF 6.7 1区医学 Q1 NEUROSCIENCES

NPJ Parkinson's Disease Pub Date : 2025-07-03 DOI:10.1038/s41531-025-01044-6

Wen Chen, Haobo Wang, Xiang Ye, Xingkai Hao, Fujie Yan, Jian Wu, Danyang Li, Yan Wang, Lizhou Xu

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引用次数: 0

Abstract

Plant-derived extracellular vesicles (EVs) show health benefits. Gardenia jasminoides Ellis, known for its neuroprotective properties, lacks therapeutic investigation on gardenia-derived extracellular vesicles (GDEVs). This study investigated the value of GDEVs in Parkinson’s disease (PD) using rotenone (Rot)-induced Parkinsonism models in dopaminergic PC12 neuron cells and Caenorhabditis elegans. PD features apoptosis in dopaminergic neurons, while GDEVs alleviate PD by mitigating mitochondrial-mediated apoptosis. Specifically, GDEVs improve Rot-induced mitochondrial dysfunction to reduce cytochrome C release and apoptosis. Consequently, GDEVs reduce the risk of PD by lowering α-synuclein levels and regulating dopamine release. RNA sequencing and subsequent studies showed that GDEVs reduce p38 MAPK and p53 phosphorylation levels, and increase the Bcl-2/Bax ratio to prevent apoptosis in PC12 cells. In Caenorhabditis elegans, we verified that GDEVs reduce PD progression by increasing dopaminergic neurons using BZ555 mutants, and enhance dopamine release and motility. This study highlights the therapeutic potential of GDEVs in preventing neurodegenerative diseases.

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栀子源性细胞外囊泡对多巴胺能神经元凋亡介导的帕金森病的治疗作用

植物来源的细胞外囊泡（EVs）显示出健康益处。栀子花以其神经保护特性而闻名，但其细胞外囊泡（GDEVs）的治疗性研究缺乏。本研究利用鱼藤酮（rotenone, Rot）诱导的帕金森病模型（多巴胺能PC12神经元细胞和秀丽隐杆线虫）研究GDEVs在帕金森病（PD）中的价值。PD以多巴胺能神经元凋亡为特征，而GDEVs通过减轻线粒体介导的凋亡来缓解PD。具体来说，GDEVs改善rot诱导的线粒体功能障碍，减少细胞色素C的释放和细胞凋亡。因此，GDEVs通过降低α-突触核蛋白水平和调节多巴胺释放来降低PD的风险。RNA测序及后续研究表明，GDEVs可降低p38 MAPK和p53磷酸化水平，提高Bcl-2/Bax比值，从而阻止PC12细胞凋亡。在秀丽隐杆线虫中，我们证实GDEVs通过增加BZ555突变体的多巴胺能神经元，并增强多巴胺释放和运动性，从而减少PD的进展。这项研究强调了GDEVs在预防神经退行性疾病方面的治疗潜力。

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来源期刊

NPJ Parkinson's Disease Medicine-Neurology (clinical)

CiteScore

9.80

自引率

5.70%

发文量

156

审稿时长

11 weeks

期刊介绍： npj Parkinson's Disease is a comprehensive open access journal that covers a wide range of research areas related to Parkinson's disease. It publishes original studies in basic science, translational research, and clinical investigations. The journal is dedicated to advancing our understanding of Parkinson's disease by exploring various aspects such as anatomy, etiology, genetics, cellular and molecular physiology, neurophysiology, epidemiology, and therapeutic development. By providing free and immediate access to the scientific and Parkinson's disease community, npj Parkinson's Disease promotes collaboration and knowledge sharing among researchers and healthcare professionals.