{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:39:59Z","timestamp":1788280799328,"version":"build-2803163510"},"reference-count":272,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education","doi-asserted-by":"publisher","award":["FRGS\/1\/2023\/SKK10\/UKM\/03\/2"],"award-info":[{"award-number":["FRGS\/1\/2023\/SKK10\/UKM\/03\/2"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Biology"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a disabling neurodegenerative disorder that is defined by progressive loss of dopaminergic neurons in the substantia nigra, deposition of \u03b1-synuclein aggregates, and chronic neuroinflammation. While symptomatic therapies have evolved, disease-modifying therapies remain elusive. Extracellular vesicles (EVs), particularly those derived from mesenchymal stem cells (MSC-EVs), have emerged as promising therapeutic agents because they possess a natural ability to cross the blood\u2013brain barrier and deliver bioactive cargo. Herein, we review the dual-edged function of EVs in PD pathogenesis: facilitating the transfer of toxic \u03b1-synuclein while also conferring neuroprotective signals through MSC-EVs. We outline the mechanisms of MSC-EV-mediated neuroprotection that include the regulation of oxidative stress, neuroinflammation, and autophagy. We also emphasize new nanocarrier systems designed to bypass delivery challenges in PD therapy. While preclinical studies are extremely encouraging, significant issues regarding scalability, standardization, and clinical translation must be resolved before realizing the ultimate therapeutic potential of EV-based and nanocarrier-based approaches to PD.<\/jats:p>","DOI":"10.3390\/biology14101349","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T09:38:08Z","timestamp":1759397888000},"page":"1349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Bench to Brain: Translating EV and Nanocarrier Research into Parkinson\u2019s Disease Therapies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-2786","authenticated-orcid":false,"given":"Barathan","family":"Muttiah","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Atiqah Haizum","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S1474-4422(25)00033-X","article-title":"Advances in diagnosis, classification, and management of pain in Parkinson\u2019s disease","volume":"24","author":"Tinazzi","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1111\/febs.14607","article-title":"Determinants of dopaminergic neuron loss in Parkinson\u2019s disease","volume":"285","author":"Surmeier","year":"2018","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pe\u00f1a-Zelayeta, L., Delgado-Minjares, K.M., Villegas-Rojas, M.M., Le\u00f3n-Arcia, K., Santiago-Balmaseda, A., Andrade-Guerrero, J., P\u00e9rez-Segura, I., Ortega-Robles, E., Soto-Rojas, L.O., and Arias-Carri\u00f3n, O. 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