ArticleThe Journal of clinical investigation2021
Aberrant oligodendroglial LDL receptor orchestrates demyelination in chronic cerebral ischemia.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Chronic Cerebral Hypoxia and Cognitive Impairment: A Systematic Review and Meta-Analysis Based on Chronic Mountain Sickness, Anemia, Chronic Obstructive Pulmonary Disease, and Obstructive Sleep Apnea.CNS neuroscience & therapeutics · 2026Pooled it
- Nanoscale magnesium hydride alleviates hypoxia-induced myelination deficits in zebrafish.Medical gas research · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- The Hypothesis of Myelinodegeneration as an Initial Risk of Neuropathic Pain.Neuroscience bulletin · 2026Review
- Gut Lachnospiraceae improves white matter injury-related cognitive decline by increasing L-arginine.Cellular & molecular biology letters · 2026Article
- Systemic delivery of anti-sense oligonucleotide targeting α-synuclein for treatment in a mouse model of multiple system atrophy.Frontiers in aging neuroscience · 2026Article
- White Matter Microstructural Injury in Patients With Acute Single Subcortical Infarction: A Preliminary Tract-Based Spatial Statistics With Atlas-Based Analysis.Neural plasticity · 2026Article
- Median nerve electrical stimulation promotes myelin regeneration through regulating miR-1-3p/BDNF/TrkB-MAPK pathway in a transient cerebral ischemia rat model.Frontiers in behavioral neuroscience · 2026Article
- Caveolin-1 Regulates Ultrastructural Alterations of Astrocytes in Chronic Cerebral Hypoperfusion.Inflammation · 2025Article
- TREML2 Modulates Microglial Phagocytosis of Myelin Debris via TLR9 in Chronic Cerebral Ischemia.Inflammation · 2025Article
- Systemic delivery of anti-sense oligonucleotide targeting a-synuclein for the treatment of multiple system atrophy.Research square · 2025Article
- Paranodal instability driven by axonal mitochondrial accumulation in ischemic demyelination and cognitive decline.Molecular psychiatry · 2025Article
- Myelin dysfunction in aging and brain disorders: mechanisms and therapeutic opportunities.Molecular neurodegeneration · 2025Review
- Article
- Blood Lipid Levels and the Severity of Guillain-Barré Syndrome: A Single-Center Retrospective Cohort Study.Neurology research international · 2025Article
- Review
- STING orchestrates microglia polarization via interaction with LC3 in autophagy after ischemia.Cell death & disease · 2024Article
- EAAT3 impedes oligodendrocyte remyelination in chronic cerebral hypoperfusion-induced white matter injury.CNS neuroscience & therapeutics · 2024Article
- Early exercise intervention promotes myelin repair in the brains of ischemic rats by inhibiting the MEK/ERK pathway.Translational neuroscience · 2024Article
- Possible Occurrence of Delayed Leukoencephalopathy Following Acute Ischemic Stroke With Large-Vessel Occlusion.Stroke (Hoboken, N.J.) · 2024Article
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oligodendrocytes express low-density lipoprotein receptor (LDLR) to endocytose cholesterol for the maintenance of adulthood myelination. However, the potential role of LDLR in chronic cerebral ischemia-related demyelination remains unclear. We used bilateral carotid artery stenosis (BCAS) to induce sustained cerebral ischemia in mice. This hypoxic-ischemic injury caused a remarkable decrease in oligodendroglial LDLR, with impaired oligodendroglial differentiation and survival. Oligodendroglial cholesterol levels, however, remained unchanged. Mouse miR-344e-3p and the human homolog miR-410-3p, 2 miRNAs directly targeting Ldlr, were identified in experimental and clinical leukoaraiosis and were thus implicated in the LDLR reduction. Lentiviral delivery of LDLR ameliorated demyelination following chronic cerebral ischemia. By contrast, Ldlr-/- mice displayed inadequate myelination in the corpus callosum. Ldlr-/- oligodendrocyte progenitor cells (OPCs) exhibited reduced ability to differentiate and myelinate axons in vitro. Transplantation with Ldlr-/- OPCs could not rescue the BCAS-induced demyelination. Such LDLR-dependent myelin restoration might involve a physical interaction of the Asn-Pro-Val-Tyr (NPVY) motif with the phosphotyrosine binding domain of Shc, which subsequently activated the MEK/ERK pathway. Together, our findings demonstrate that the aberrant oligodendroglial LDLR in chronic cerebral ischemia impairs myelination through intracellular signal transduction. Preservation of oligodendroglial LDLR may provide a promising approach to treat ischemic demyelination.
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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.