ArticleCell death & disease2021
Fibrillar α-synuclein induces neurotoxic astrocyte activation via RIP kinase signaling and NF-κB.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 86 citations in OpenAlex.
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Post-translational modifications in Neuroimmune cells during neuroinflammation: integrated regulatory networks and therapeutic opportunities.Biology direct · 2026Review
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- Reactive astrocytes mediate toxicity in iPSC derived dopaminergic neurons.NPJ Parkinson's disease · 2026Article
- Microglia-derived extracellular vesicles attenuate acute a-synuclein induced astrocyte inflammation.bioRxiv : the preprint server for biology · 2026Article
- A microbiome quantitative trait locus in SLC39A8 modulates disease severity in synucleinopathy-induced models of Parkinson's disease.Human molecular genetics · 2026Article
- Ultrasonic repression of TRPA1-dependent astrocyte reactivity confers neuroprotection in models of Lewy body dementia.Translational neurodegeneration · 2026Article
- Microglia, Astrocytes, and Oligodendrocytes in Parkinson's Disease: Neuroinflammatory Crosstalk and Emerging Therapeutic Strategies.Biomolecules · 2026Review
- Interconnected roles of astrocytes and the blood-brain barrier in Parkinson's disease: pathological evidence, mechanistic insights, and knowledge gaps.Frontiers in aging neuroscience · 2026Review
- STN-DBS exerts neuroprotection and anti-inflammatory effects in a Parkinson's disease rat model.Frontiers in immunology · 2026Article
- Ketogenic diet and Parkinson's disease.Frontiers in molecular neuroscience · 2026Review
- Sphingomyelin regulates astrocyte activity by regulating NF-κB signaling via HDAC1/3 expression.Journal of lipid research · 2025Article
- The mCells · 2025Review
- Tripartite Interaction of Epigenetic Regulation, Brain Aging, and Neuroinflammation: Mechanistic Insights and Therapeutic Implications.Epigenomes · 2025Review
- Recent Advances in Autophagy and Immunotherapy for the Clearance of Aggregated α-Synuclein in Parkinson's Disease.Aging and disease · 2025Review
- Astrocytic RIPK3 exerts protective anti-inflammatory activity in mice with viral encephalitis by transcriptional induction of serpins.Science signaling · 2025Article
- Heterogeneity of Astrocyte Reactivity.Annual review of neuroscience · 2025Review
- Extracellular ATP regulates phagocytic activity, mitochondrial respiration, and cytokine secretion of human astrocytic cells.Purinergic signalling · 2025Article
- α-Synuclein in Parkinson's Disease: From Bench to Bedside.Medicinal research reviews · 2025Review
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 1 institution in 1 country.
Funding
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the death of midbrain dopamine neurons. The pathogenesis of PD is poorly understood, though misfolded and/or aggregated forms of the protein α-synuclein have been implicated in several neurodegenerative disease processes, including neuroinflammation and astrocyte activation. Astrocytes in the midbrain play complex roles during PD, initiating both harmful and protective processes that vary over the course of the disease. However, despite their significant regulatory roles during neurodegeneration, the cellular and molecular mechanisms that promote pathogenic astrocyte activity remain mysterious. Here, we show that α-synuclein preformed fibrils (PFFs) induce pathogenic activation of human midbrain astrocytes, marked by inflammatory transcriptional responses, downregulation of phagocytic function, and conferral of neurotoxic activity. These effects required the necroptotic kinases RIPK1 and RIPK3, but were independent of MLKL and necroptosis. Instead, both transcriptional and functional markers of astrocyte activation occurred via RIPK-dependent activation of NF-κB signaling. Our study identifies a previously unknown function for α-synuclein in promoting neurotoxic astrocyte activation, as well as new cell death-independent roles for RIP kinase signaling in the regulation of glial cell biology and neuroinflammation. Together, these findings highlight previously unappreciated molecular mechanisms of pathologic astrocyte activation and neuronal cell death with implications for Parkinsonian neurodegeneration.
Indexed as
Identifiers
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.