ArticleThe Journal of experimental medicine2021
Endothelial LRP1 protects against neurodegeneration by blocking cyclophilin A.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 122 citations in OpenAlex.
- Unravelling Ovarian Cancer: an analysis of the Influence of LRP1 and PAI1 Genetic Variations.Biochemical genetics · 2026Article
- Luteolin Improves BBB Integrity Following Ischemic Stroke Injury by Downregulating the Expression of LRP1 and MMP9.Phytotherapy research : PTR · 2026Article
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Research Progress on the Molecular Mechanism of LRP1 and TGFβ-PDGFRβ Signaling Network in Atherosclerosis and Vascular Remodeling.International journal of molecular sciences · 2026Review
- Periventricular gradient of normal-appearing white matter in normal aging and multiple neurological diseases.Journal of advanced research · 2026Article
- Anti-Inflammatory and Antioxidant Effects of ω-3 Polyunsaturated Fatty Acids on Astrocytes and Their Implications for the Blood-Brain Barrier's Integrity and Function.International journal of molecular sciences · 2026Review
- Modulating LRP1 Pathways in Alzheimer's Disease: Mechanistic Insights and Emerging Therapies.Molecular neurobiology · 2026Review
- Sialylation patterns in cerebral amyloid angiopathy.Brain pathology (Zurich, Switzerland) · 2026Article
- Construction of an In Vitro Blood-Brain Barrier Micro-Organoid Model Using Decellularized Squid Mantle Scaffold Film.Journal of functional biomaterials · 2026Article
- LRP1 as a potential diagnostic and immunomodulatory target in endometriosis: evidence from multi-omics and single-cell analyses.Frontiers in immunology · 2026Article
- Glycogen synthase kinase-3 activation and dysregulation of amyloid transport receptors expression and shedding in HIV-induced Alzheimer's disease-like pathology: modulatory effects of CCR5 antagonists.Acta neuropathologica communications · 2025Article
- Mechanisms of high-density lipoprotein in regulating blood-brain barrier function: insights and implications.Fluids and barriers of the CNS · 2025Review
- Single-cell stemness analysis highlights Midkine-LRP1 pathway and identifies new bladder cancer subtypes.Cancer cell international · 2025Article
- Targeting Transferrin Receptor 1 for Enhancing Drug Delivery Through the Blood-Brain Barrier for Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Rapid amyloid-β clearance and cognitive recovery through multivalent modulation of blood-brain barrier transport.Signal transduction and targeted therapy · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Endothelial delivery of simvastatin by LRP1-targeted nanoparticles ameliorates pathogenesis of alzheimer's disease in a mouse model.Alzheimer's research & therapy · 2025Article
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.The Lancet. Neurology · 2025Review
- APOE4 and sedentary lifestyle synergistically impair neurovascular function in the visual cortex of awake mice.Communications biology · 2025Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
The low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic and cell signaling transmembrane protein. Endothelial LRP1 clears proteinaceous toxins at the blood-brain barrier (BBB), regulates angiogenesis, and is increasingly reduced in Alzheimer's disease associated with BBB breakdown and neurodegeneration. Whether loss of endothelial LRP1 plays a direct causative role in BBB breakdown and neurodegenerative changes remains elusive. Here, we show that LRP1 inactivation from the mouse endothelium results in progressive BBB breakdown, followed by neuron loss and cognitive deficits, which is reversible by endothelial-specific LRP1 gene therapy. LRP1 endothelial knockout led to a self-autonomous activation of the cyclophilin A-matrix metalloproteinase-9 pathway in the endothelium, causing loss of tight junctions underlying structural BBB impairment. Cyclophilin A inhibition in mice with endothelial-specific LRP1 knockout restored BBB integrity and reversed and prevented neuronal loss and behavioral deficits. Thus, endothelial LRP1 protects against neurodegeneration by inhibiting cyclophilin A, which has implications for the pathophysiology and treatment of neurodegeneration linked to vascular dysfunction.
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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.