ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2018
Combined Active Humoral and Cellular Immunization Approaches for the Treatment of Synucleinopathies.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- The Progress of Active Immunotherapy for Parkinson's Disease.International journal of molecular sciences · 2026Review
- White Blood Cells in Neurodegenerative Diseases in the Context of Neuroinflammation.Molecular neurobiology · 2025Review
- Parkinson's disease: genetics and neuroinflammatory insights.Inflammopharmacology · 2025Review
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- The immune system in Parkinson's disease: what we know so far.Brain : a journal of neurology · 2024Review
- Rational design of structure-based vaccines targeting misfolded alpha-synuclein conformers of Parkinson's disease and related disorders.Bioengineering & translational medicine · 2024Article
- Neurovascular and immune factors of vulnerability of substantia nigra dopaminergic neurons in non-human primates.NPJ Parkinson's disease · 2024Article
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
- Pathological mechanisms of neuroimmune response and multitarget disease-modifying therapies of mesenchymal stem cells in Parkinson's disease.Stem cell research & therapy · 2023Review
- Antiparkinsonian Agents in Investigational Polymeric Micro- and Nano-Systems.Pharmaceutics · 2022Review
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Alpha-Synuclein Aggregation Pathway in Parkinson's Disease: Current Status and Novel Therapeutic Approaches.Cells · 2022Review
- Article
- NANOTECHNOLOGY-MEDIATED THERAPEUTIC STRATEGIES AGAINST SYNUCLEINOPATHIES IN NEURODEGENERATIVE DISEASE.Current opinion in chemical engineering · 2021Article
- Alpha-Synuclein Induced Immune Cells Activation and Associated Therapy in Parkinson's Disease.Frontiers in aging neuroscience · 2021Review
- Treating Parkinson's Disease with Antibodies: Previous Studies and Future Directions.Journal of Parkinson's disease · 2021Review
- Targeting α-synuclein by PD03 AFFITOPE® and Anle138b rescues neurodegenerative pathology in a model of multiple system atrophy: clinical relevance.Translational neurodegeneration · 2020Article
- Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models.Journal of neuroinflammation · 2020Article
- Immunotherapies for Aging-Related Neurodegenerative Diseases-Emerging Perspectives and New Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Dementia with Lewy bodies, Parkinson's disease, and Multiple System Atrophy are age-related neurodegenerative disorders characterized by progressive accumulation of α-synuclein (α-syn) and jointly termed synucleinopathies. Currently, no disease-modifying treatments are available for these disorders. Previous preclinical studies demonstrate that active and passive immunizations targeting α-syn partially ameliorate behavioral deficits and α-syn accumulation; however, it is unknown whether combining humoral and cellular immunization might act synergistically to reduce inflammation and improve microglial-mediated α-syn clearance. Since combined delivery of antigen plus rapamycin (RAP) in nanoparticles is known to induce antigen-specific regulatory T cells (Tregs), we adapted this approach to α-syn using the antigen-presenting cell-targeting glucan microparticle (GP) vaccine delivery system. PDGF-α-syn transgenic (tg) male and female mice were immunized with GP-alone, GP-α-syn (active humoral immunization), GP+RAP, or GP+RAP/α-syn (combined active humoral and Treg) and analyzed using neuropathological and biochemical markers. Active immunization resulted in higher serological total IgG, IgG1, and IgG2a anti-α-syn levels. Compared with mice immunized with GP-alone or GP-α-syn, mice vaccinated with GP+RAP or GP+RAP/α-syn displayed increased numbers of CD25-, FoxP3-, and CD4-positive cells in the CNS. GP-α-syn or GP+RAP/α-syn immunizations resulted in a 30-45% reduction in α-syn accumulation, neuroinflammation, and neurodegeneration. Mice immunized with GP+RAP/α-syn further rescued neurons and reduced neuroinflammation. Levels of TGF-β1 were increased with GP+RAP/α-syn immunization, while levels of TNF-α and IL-6 were reduced. We conclude that the observed effects of GP+RAP/α-syn immunization support the hypothesis that cellular immunization may enhance the effects of active immunotherapy for the treatment of synucleinopathies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.