ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Antibody-aided clearance of extracellular α-synuclein prevents cell-to-cell aggregate transmission.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 208 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
208 citing papers in PubMed, 1 synthesis or guideline pooled it, 330 citations in OpenAlex.
- Effectiveness of Acupuncture in the Treatment of Parkinson's Disease: An Overview of Systematic Reviews.Frontiers in neurology · 2020Pooled it
- Phase 1, randomized trials of MEDI1341: cerebrospinal fluid free α-synuclein lowered by >50.Brain communications · 2025Trial
- Target engagement and immunogenicity of an active immunotherapeutic targeting pathological α-synuclein: a phase 1 placebo-controlled trial.Nature medicine · 2024Trial
- Randomized phase I clinical trial of anti-α-synuclein antibody BIIB054.Movement disorders : official journal of the Movement Disorder Society · 2019Trial
- Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial.JAMA neurology · 2018Trial
- First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers.Movement disorders : official journal of the Movement Disorder Society · 2017Trial
- Cell-based immunotherapy for neurodegenerative disease: A promising avenue.Neural regeneration research · 2026Article
- The irony of Parkinson's disease: Converging mechanisms of redox imbalance and ferroptosis.Redox biology · 2026Review
- Clinical innovations and future directions of nanoparticles in the treatment of psychiatric and neurological disorders.Molecular psychiatry · 2026Review
- Identification of KHS-101 as a Transcription Factor EB Activator to Promote α-Synuclein Degradation.International journal of molecular sciences · 2026Article
- A brain-shuttled antibody targeting alpha synuclein aggregates for the treatment of synucleinopathies.NPJ Parkinson's disease · 2025Article
- Monitoring and investigation to control the brain network disease under immunotherapy by using fractional operator.Scientific reports · 2025Article
- Crossing Barriers: Advancements in Macromolecular Therapeutics for Neurodegenerative Diseases and Strategies to Overcome the Blood-Brain Barrier.ACS pharmacology & translational science · 2025Review
- Proteolytic therapeutic modalities for amyloidoses: Insights into immunotherapy, PROTAC, and photo-oxygenation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- A brain-penetrant bispecific antibody lowers oligomeric alpha-synuclein and activates microglia in a mouse model of alpha-synuclein pathology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- The interaction of tPA with NMDAR1 drives neuroinflammation and neurodegeneration in α-synuclein-mediated neurotoxicity.Journal of neuroinflammation · 2025Article
- α-Synuclein pathology as a target in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- An update on immune-based alpha-synuclein trials in Parkinson's disease.Journal of neurology · 2024Review
- Targeting Protein Misfolding and Aggregation as a Therapeutic Perspective in Neurodegenerative Disorders.International journal of molecular sciences · 2024Review
- α-Synuclein disrupts microglial autophagy through STAT1-dependent suppression of Ulk1 transcription.Journal of neuroinflammation · 2024Article
148 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Abnormal deposition and intercellular propagation of α-synuclein plays a central role in the pathogenesis of disorders such as Parkinson's Disease (PD) and dementia with Lewy bodies (DLB). Previous studies demonstrated that immunization against α-synuclein resulted in reduced α-synuclein accumulation and synaptic loss in a transgenic (tg) mouse model, highlighting the potential for immunotherapy. However, the mechanism by which immunization prevents synucleinopathy-associated deficits remains unknown. Here, we show that antibodies against α-synuclein specifically target and aid in clearance of extracellular α-synuclein proteins by microglia, thereby preventing their actions on neighboring cells. Antibody-assisted clearance occurs mainly in microglia through the Fcγ receptor, and not in neuronal cells or astrocytes. Stereotaxic administration of antibody into the brains of α-synuclein tg mice prevented neuron-to-astroglia transmission of α-synuclein and led to increased localization of α-synuclein and the antibody in microglia. Furthermore, passive immunization with α-synuclein antibody reduced neuronal and glial accumulation of α-synuclein and ameliorated neurodegeneration and behavioral deficits associated with α-synuclein overexpression. These findings provide an underlying mechanistic basis for immunotherapy for PD/DLB and suggest extracellular forms of α-synuclein as potential therapeutic targets.
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What OpenQuestion holds
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.