ArticleNature communications2021
NEK1-mediated retromer trafficking promotes blood-brain barrier integrity by regulating glucose metabolism and RIPK1 activation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- A2 astrocyte polarization mediates ketogenic diet protection of blood-central nervous system barriers in experimental autoimmune encephalomyelitis.Neural regeneration research · 2026Article
- TAF1 aggravates ferroptosis by promoting the ubiquitin-mediated degradation of nuclear GPX4.Journal of Zhejiang University. Science. B · 2026Article
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Progress in peptide and protein therapeutics: Challenges and strategies.Acta pharmaceutica Sinica. B · 2025Review
- NEK Family Kinases: Structure, Function, and Role in Disease.Biomolecules · 2025Review
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- MTFR1 phosphorylation-activated adaptive mitochondrial fusion is essential for colon cancer cell survival during glucose deprivation.Neoplasia (New York, N.Y.) · 2025Article
- Advances in the Study of Necroptosis in Vascular Dementia: Focus on Blood-Brain Barrier and Neuroinflammation.CNS neuroscience & therapeutics · 2025Review
- Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.Nature reviews. Neurology · 2025Review
- Clinicopathological analysis of NEK1 variants in amyotrophic lateral sclerosis.Brain pathology (Zurich, Switzerland) · 2025Article
- Necroptosis in vascular cognitive impairment: mechanisms and therapeutic potential.Frontiers in aging neuroscience · 2025Review
- The emerging role of Never-in-Mitosis A - Related Kinases in the endothelium.The international journal of biochemistry & cell biology · 2024Review
- Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.Communications biology · 2024Article
- The Mitochondrial Connection: The Nek Kinases' New Functional Axis in Mitochondrial Homeostasis.Cells · 2024Review
- Serum Proteomics Identified TAFI as a Potential Molecule Facilitating the Migration of Peripheral Monocytes to Damaged White Matter During Chronic Cerebral Hypoperfusion.Neurochemical research · 2024Article
- RIPK1 activation in Mecp2-deficient microglia promotes inflammation and glutamate release in RTT.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Die Hard: Necroptosis and its Impact on Age-Dependent Neuroinflammatory Diseases.Frontiers in cell death · 2024Article
- Neuroprotective Mechanism of MOTS-c in TBI Mice: Insights from Integrated Transcriptomic and Metabolomic Analyses.Drug design, development and therapy · 2024Article
- Elevated peripheral levels of receptor-interacting protein kinase 1 (RIPK1) and IL-8 as biomarkers of human amyotrophic lateral sclerosis.Signal transduction and targeted therapy · 2023Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss-of-function mutations in NEK1 gene, which encodes a serine/threonine kinase, are involved in human developmental disorders and ALS. Here we show that NEK1 regulates retromer-mediated endosomal trafficking by phosphorylating VPS26B. NEK1 deficiency disrupts endosomal trafficking of plasma membrane proteins and cerebral proteome homeostasis to promote mitochondrial and lysosomal dysfunction and aggregation of α-synuclein. The metabolic and proteomic defects of NEK1 deficiency disrupts the integrity of blood-brain barrier (BBB) by promoting lysosomal degradation of A20, a key modulator of RIPK1, thus sensitizing cerebrovascular endothelial cells to RIPK1-dependent apoptosis and necroptosis. Genetic inactivation of RIPK1 or metabolic rescue with ketogenic diet can prevent postnatal lethality and BBB damage in NEK1 deficient mice. Inhibition of RIPK1 reduces neuroinflammation and aggregation of α-synuclein in the brains of NEK1 deficient mice. Our study identifies a molecular mechanism by which retromer trafficking and metabolism regulates cerebrovascular integrity, cerebral proteome homeostasis and RIPK1-mediated neuroinflammation.
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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.