ArticleJournal of neuroinflammation2021
Alpha-synuclein activates the classical complement pathway and mediates complement-dependent cell toxicity.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- The mitophagy-inflammasome axis: a shared pathological hub in Alzheimer's and Parkinson's diseases.Translational neurodegeneration · 2026Review
- Complement dysregulation during the early phases of synucleinopathy.Acta neuropathologica · 2026Article
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- Unique nigral and cortical pathways implicated by epigenomic and transcriptional analyses in rotenone Parkinson's model.NPJ Parkinson's disease · 2025Article
- Advantages of using complement components in preventive and therapeutic vaccine strategies for infectious and non-infectious diseases.Journal of the Royal Society, Interface · 2025Review
- Comparison of inflammatory biomarker levels in neurodegenerative proteinopathies: a case-control study.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Chronic stress induces depression-like behaviors and Parkinsonism via upregulating α-synuclein.NPJ Parkinson's disease · 2025Article
- Complement C4 exacerbates astrocyte-mediated neuroinflammation and promotes α-synuclein pathology in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- The Spectrum of Cognitive Impairment in Atypical Parkinsonism Syndromes: A Comprehensive Review of Current Understanding and Research.Diseases (Basel, Switzerland) · 2025Review
- Non-canonical Roles of Complement in the CNS: From Synaptic Organizer to Presynaptic Modulator of Glutamate Transmission.Current neuropharmacology · 2025Review
- Glycine-to-aspartic acid mutation at codon 51 inBrain communications · 2025Article
- (Re)building the nervous system: A review of neuron-glia interactions from development to disease.Journal of neurochemistry · 2025Review
- Proximity Elongation Assay and ELISA for the Identification of Serum Diagnostic Biomarkers in Parkinson's Disease and Progressive Supranuclear Palsy.International journal of molecular sciences · 2024Article
- The Pathobiology of Behavioral Changes in Multiple System Atrophy: An Update.International journal of molecular sciences · 2024Review
- Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity.Cell & bioscience · 2024Article
- The complement system in neurodegenerative diseases.Clinical science (London, England : 1979) · 2024Article
- Infectious Diseases.Advances in neurobiology · 2024Review
- Amyloid-βiScience · 2023Article
- Mild cognitive impairment in multiple system atrophy: a brain network disorder.Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- Botulinum neurotoxin A ameliorates depressive-like behavior in a reserpine-induced Parkinson's disease mouse model via suppressing hippocampal microglial engulfment and neuroinflammation.Acta pharmacologica Sinica · 2023Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundSynucleinopathies are characterized by neurodegeneration and deposition of the presynaptic protein α-synuclein in pathological protein inclusions. Growing evidence suggests the complement system not only has physiological functions in the central nervous system, but also is involved in mediating the pathological loss of synapses in Alzheimer's disease. However, it is not established whether the complement system has a similar role in the diseases Parkinson's disease, Dementia with Lewy bodies, and multiple system atrophy (MSA) that are associated with α-synuclein aggregate pathology.
methodsTo investigate if the complement system has a pathological role in synucleinopathies, we assessed the effect of the complement system on the viability of an α-synuclein expressing cell model and examined direct activation of the complement system by α-synuclein in a plate-based activation assay. Finally, we investigated the levels of the initiator of the classical pathway, C1q, in postmortem brain samples from MSA patients.
resultsWe demonstrate that α-synuclein activates the classical complement pathway and mediates complement-dependent toxicity in α-synuclein expressing SH-SY5Y cells. The α-synuclein-dependent cellular toxicity was rescued by the complement inhibitors RaCI (inhibiting C5) and Cp20 (inhibiting C3). Furthermore, we observed a trend for higher levels of C1q in the putamen of MSA subjects than that of controls.
conclusionα-Synuclein can activate the classical complement pathway, and the complement system is involved in α-synuclein-dependent cellular cytotoxicity suggesting the system could play a prodegenerative role in synucleinopathies.
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