{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:16:39Z","timestamp":1789082199483,"version":"build-2803163510"},"reference-count":135,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a multifactorial neurodegenerative disorder defined by nigrostriatal dopaminergic neuron loss and the pathological aggregation of alpha synuclein, yet current clinical interventions remain largely symptomatic and fail to alter long-term disease progression. Emerging evidence demonstrates that immune dysregulation and chronic neuroinflammation contribute significantly to PD pathology, supporting the rationale for active immunotherapy as a disease modifying strategy. This review examines contemporary active immunotherapy platforms including peptide vaccines, genetic vaccination strategies, and antigen sensitized dendritic cell (DC) vaccines with emphasis on the dual capacity of DC based approaches to enhance pathological protein clearance and restore immune homeostasis. Technical limitations and translational barriers are evaluated such as immune heterogeneity among patients, the blood\u2013brain barrier, and variability in DC vaccine manufacturing. Finally, future research directions are proposed including individualized immunologic profiling for treatment stratification, long-acting immunomodulatory formulations, and development of isoform specific DC powder vaccines capable of targeted alpha synuclein engagement. Collectively, these advances highlight active immunotherapy as a promising pathway toward disease modification in Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms27052194","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:33:02Z","timestamp":1772101982000},"page":"2194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Progress of Active Immunotherapy for Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Daniel","family":"Busot","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Arts & Sciences, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-6859","authenticated-orcid":false,"given":"Darrell","family":"Sawmiller","sequence":"additional","affiliation":[{"name":"MegaNano BioTech, Inc., 3802 Spectrum Blvd., Suite 122, Tampa, FL 33612, USA"},{"name":"MegaNano Diagnostics, Inc., 3802 Spectrum Blvd., Suite 149, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-6401","authenticated-orcid":false,"given":"Chuanhai","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"},{"name":"USF Health Byrd Alzheimer\u2019s Institute, University of South Florida, Tampa, FL 33613, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1087753","article-title":"Molecular pathways of neurodegeneration in Parkinson\u2019s disease","volume":"302","author":"Dawson","year":"2003","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1126\/science.1065931","article-title":"Neurobiology. 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