ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson's disease-like models.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers, 1 of them a synthesis that pooled it.
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Who cites it
190 citing papers in PubMed, 1 synthesis or guideline pooled it, 310 citations in OpenAlex.
- The Effect of Aggregated Alpha Synuclein on Synaptic and Axonal Proteins in Parkinson's Disease-A Systematic Review.Biomolecules · 2022Pooled it
- Phase 1, randomized trials of MEDI1341: cerebrospinal fluid free α-synuclein lowered by >50.Brain communications · 2025Trial
- 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
- The irony of Parkinson's disease: Converging mechanisms of redox imbalance and ferroptosis.Redox biology · 2026Review
- Modulation of biomolecular condensation of alpha-synuclein variants by eprodisate.Communications chemistry · 2026Article
- Insight into the Neuroprotective Mechanisms of Resveratrol: Inhibition of Alpha-Synuclein Fibrillation and its Role in Mitigating Toxicity.Cell biochemistry and biophysics · 2026Article
- Reliable repurposing of the antibody interactome inside the cell.Nature communications · 2026Article
- C-terminus-dependent detection of lysosomal alpha-synuclein in nigral Parkinson's disease human brain neurons.Molecular neurodegeneration · 2025Article
- "Coordination of Anle138b to Silver Results in Selective Reduction of a C-terminal truncated Alpha-synuclein Protein and Increased Aggregate Size."bioRxiv : the preprint server for biology · 2025Article
- Monoclonal Antibodies as Therapeutic Agents in Autoimmune and Neurodegenerative Diseases of the Central Nervous System: Current Evidence on Molecular Mechanisms and Future Directions.International journal of molecular sciences · 2025Review
- A Review of the Recent Advances in the Pharmacological Management of Parkinson's Disease.Cureus · 2025Review
- A brain-shuttled antibody targeting alpha synuclein aggregates for the treatment of synucleinopathies.NPJ Parkinson's disease · 2025Article
- Immunization targeting diseased proteins in synucleinopathy and tauopathy: insights from clinical trials.Translational neurodegeneration · 2025Review
- Alpha-synuclein pathology and Parkinson's disease-related olfactory dysfunctions: an update on preclinical models and therapeutic approaches.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- α-Synuclein in Parkinson's Disease: From Bench to Bedside.Medicinal research reviews · 2025Review
- Alpha-Synuclein Pathophysiology in Neurodegenerative Disorders: A Review Focusing on Molecular Mechanisms and Treatment Advances in Parkinson's Disease.Cellular and molecular neurobiology · 2025Review
- Prasinezumab slows motor progression in Parkinsons disease: beyond the clinical data.NPJ Parkinson's disease · 2025Review
- An update on immune-based alpha-synuclein trials in Parkinson's disease.Journal of neurology · 2024Review
- The small molecule ZPD-2 inhibits the aggregation and seeded polymerisation of C-terminally truncated α-Synuclein.The FEBS journal · 2024Article
130 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are common neurodegenerative disorders of the aging population, characterized by progressive and abnormal accumulation of α-synuclein (α-syn). Recent studies have shown that C-terminus (CT) truncation and propagation of α-syn play a role in the pathogenesis of PD/DLB. Therefore, we explored the effect of passive immunization against the CT of α-syn in the mThy1-α-syn transgenic (tg) mouse model, which resembles the striato-nigral and motor deficits of PD. Mice were immunized with the new monoclonal antibodies 1H7, 5C1, or 5D12, all directed against the CT of α-syn. CT α-syn antibodies attenuated synaptic and axonal pathology, reduced the accumulation of CT-truncated α-syn (CT-α-syn) in axons, rescued the loss of tyrosine hydroxylase fibers in striatum, and improved motor and memory deficits. Among them, 1H7 and 5C1 were most effective at decreasing levels of CT-α-syn and higher-molecular-weight aggregates. Furthermore, in vitro studies showed that preincubation of recombinant α-syn with 1H7 and 5C1 prevented CT cleavage of α-syn. In a cell-based system, CT antibodies reduced cell-to-cell propagation of full-length α-syn, but not of the CT-α-syn that lacked the 118-126 aa recognition site needed for antibody binding. Furthermore, the results obtained after lentiviral expression of α-syn suggest that antibodies might be blocking the extracellular truncation of α-syn by calpain-1. Together, these results demonstrate that antibodies against the CT of α-syn reduce levels of CT-truncated fragments of the protein and its propagation, thus ameliorating PD-like pathology and improving behavioral and motor functions in a mouse model of this disease.
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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.