RVG-targeted extracellular vesicles loaded with echinatin attenuate dopaminergic neurodegeneration via the IGF-2/PI3K/Akt pathway in Parkinson’s disease mice
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BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons. The development of effective neuroprotective therapies is severely hampered by the blood-brain barrier (BBB), which restricts drug delivery to the central nervous system. This study aimed to develop a novel brain-targeted nanodelivery system by functionalizing extracellular vesicles (EVs) with a rabies virus glycoprotein (RVG)-derived peptide to deliver echinatin (Echi), and to systematically evaluate its therapeutic efficacy and underlying mechanisms in a mouse model of PD. RESULTS: We successfully engineered the nanotherapeutics, termed RVG-EVs@Echi, which efficiently crossed the BBB and selectively accumulated in DA neurons and microglia following systemic administration. In a chronic MPTP-induced mouse model of PD, treatment with RVG-EVs@Echi significantly ameliorated motor deficits and rescued tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and striatum, with no detectable peripheral toxicity. Mechanistically, RVG-EVs@Echi exerted potent neuroprotective effects by upregulating insulin-like growth factor-2 (IGF-2) and activating the downstream PI3K/Akt/Nrf2 signaling cascade, which mitigated oxidative stress and neuronal apoptosis. Furthermore, integrated multi-omics analyses revealed that RVG-EVs@Echi treatment modulated metabolic profiles in the midbrain and gut, and partially restored MPTP-induced gut microbiota dysbiosis. CONCLUSIONS: This study demonstrates that RVG-EVs@Echi represents a safe, noninvasive, and effective nanotherapeutic platform for targeted brain delivery in PD. By activating the IGF-2/PI3K/Akt/Nrf2 neuroprotective pathway and modulating the gut-brain metabolic axis, this targeted delivery system presents a highly promising and translatable strategy for the treatment of PD and other neurodegenerative diseases.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- RVG-targeted extracellular vesicles loaded with echinatin attenuate dopaminergic neurodegeneration via the IGF-2/PI3K/Akt pathway in Parkinson’s disease mice
- Date Crossref
- 07/01/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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First Affiliated Hospital of Guangzhou Medical University Department of Neurology pays non établi dans la noticeÉtablissement de santé
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Guangzhou Medical University pays non établi dans la noticeUniversité ou école supérieure
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Wenzhou Medical University Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Xinjiang Medical University pays non établi dans la noticeUniversité ou école supérieure
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Second Affiliated Hospital of Xinjiang Medical University pays non établi dans la noticeUniversité ou école supérieure
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Guangdong Medical College pays non établi dans la noticeUniversité ou école supérieure
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The Clinical Medicine of Guangdong Medical University Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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School of Basic Medical Sciences Department of Physiology pays non établi dans la noticeUniversité ou école supérieure
Department of Neurology — First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University et Department of Neurology — Wenzhou Medical University, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.