ArticleProceedings of the National Academy of Sciences of the United States of America2020
NK cells clear α-synuclein and the depletion of NK cells exacerbates synuclein pathology in a mouse model of α-synucleinopathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 3 of them syntheses that pooled it.
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Who cites it
86 citing papers in PubMed, 3 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Experimental procedures for flow cytometry of wild-type mouse brain: a systematic review.Frontiers in immunology · 2023Pooled it
- Pathological Role of Natural Killer Cells in Parkinson's Disease: A Systematic Review.Frontiers in aging neuroscience · 2022Pooled it
- MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications.Frontiers in neurology · 2021Pooled it
- Benefits of Gut Microbiota Reconstitution by Beta 1,3-1,6 Glucans in Subjects with Autism Spectrum Disorder and Other Neurodegenerative Diseases.Journal of Alzheimer's disease : JAD · 2023Trial
- Monocyte markers correlate with immune and neuronal brain changes in REM sleep behavior disorder.Proceedings of the National Academy of Sciences of the United States of America · 2021Trial
- Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases.MedComm · 2026Review
- β-glucan elicits APOE-dependent peripheral trained immunity to suppress hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- Natural Killer Subset Changes and Vascular Endothelial Growth Factor-A Plasma Profile in Progressive Supranuclear Palsy: The NKscape Study.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Unconventional functions of natural killer cells in homeostasis and disease.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Peripheral immunosenescence biomarkers and longitudinal cognitive decline: a large population-based study.npj aging · 2026Article
- Peripheral Immunological Signatures of Parkinsonism: Insights from the Caribbean vs. North America.Molecular neurobiology · 2026Article
- Microglia in the crosstalk between peripheral and central nervous systems in Parkinson's disease.Translational neurodegeneration · 2025Review
- Decoding the multifaceted cellular and transcriptomic variations of natural killer cells generated from patients with Parkinson's disease.Scientific reports · 2025Article
- Biological and translational attributes of mitochondrial DNA copy number: Laboratory perspective to clinical relevance.World journal of methodology · 2025Review
- Physical activity affects DNA methylation-derived inflammation markers in a community-based Parkinson's disease study.Brain, behavior, & immunity - health · 2025Article
- Peripheral innate immunophenotype in neurodegenerative disease: blood-based profiles and links to survival.Molecular psychiatry · 2025Article
- Identification and Validation of Oxidative Stress-Related Hub Genes in Parkinson's Disease.Molecular neurobiology · 2025Article
- Alpha-Synuclein Pathophysiology in Neurodegenerative Disorders: A Review Focusing on Molecular Mechanisms and Treatment Advances in Parkinson's Disease.Cellular and molecular neurobiology · 2025Review
- Bradykinesia and postural instability in a model of prodromal synucleinopathy with α-synuclein aggregation initiated in the gigantocellular nuclei.Acta neuropathologica communications · 2025Article
- Treatment of Alzheimer's Disease subjects with expanded non-genetically modified autologous natural killer cells (SNK01): a phase I study.Alzheimer's research & therapy · 2025Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The pathological hallmark of synucleinopathies, including Lewy body dementia and Parkinson's disease (PD), is the presence of Lewy bodies, which are primarily composed of intracellular inclusions of misfolded α-synuclein (α-syn) among other proteins. α-Syn is found in extracellular biological fluids in PD patients and has been implicated in modulating immune responses in the central nervous system (CNS) and the periphery. Natural killer (NK) cells are innate effector lymphocytes that are present in the CNS in homeostatic and pathological conditions. NK cell numbers are increased in the blood of PD patients and their activity is associated with disease severity; however, the role of NK cells in the context of α-synucleinopathies has never been explored. Here, we show that human NK cells can efficiently internalize and degrade α-syn aggregates via the endosomal/lysosomal pathway. We demonstrate that α-syn aggregates attenuate NK cell cytotoxicity in a dose-dependent manner and decrease the release of the proinflammatory cytokine, IFN-γ. To address the role of NK cells in PD pathogenesis, NK cell function was investigated in a preformed fibril α-syn-induced mouse PD model. Our studies demonstrate that in vivo depletion of NK cells in a preclinical mouse PD model resulted in exacerbated motor deficits and increased phosphorylated α-syn deposits. Collectively, our data provide a role of NK cells in modulating synuclein pathology and motor symptoms in a preclinical mouse model of PD, which could be developed into a therapeutic for PD and other 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.