ArticleBrain communications2020
Neuronal megalin mediates synaptic plasticity-a novel mechanism underlying intellectual disabilities in megalin gene pathologies.
Article in Brain communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Receptor-mediated endocytosis by Megalin: Exploring its role in ligand interaction and disease mechanisms.Genes & diseases · 2026Review
- Vitamin D as a cellular endocrine system: Tissue-specific microcircuits, immune reprogramming, and metabolic resistance.iScience · 2026Review
- Intersectin1/cdc42 signaling regulates methamphetamine-induced neuronal remodeling in the hippocampus.Cellular and molecular life sciences : CMLS · 2025Article
- Transthyretin, a novel prognostic marker of POCD revealed by time-series RNA-sequencing analysis.Molecular psychiatry · 2025Article
- Microglia-Derived Vitamin D Binding Protein Mediates Synaptic Damage and Induces Depression by Binding to the Neuronal Receptor Megalin.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PCSK9 inhibitor effectively alleviated cognitive dysfunction in a type 2 diabetes mellitus rat model.PeerJ · 2024Article
- Identification of ecdysone receptor target genes in the worker honey bee brains during foraging behavior.Scientific reports · 2023Article
- Megalin Expression in Primary Oral Squamous Cell Carcinoma Is Associated with the Presence of Lymph Node Metastases, Vascular Invasion, and Lower Overall Survival.Current issues in molecular biology · 2023Article
- Low-Density Lipoprotein Receptor-Related Protein 8 at the Crossroad between Cancer and Neurodegeneration.International journal of molecular sciences · 2022Review
- The role of lipocalin 2 in brain injury and recovery after ischemic and hemorrhagic stroke.Frontiers in molecular neuroscience · 2022Review
- Transcriptomic Analysis of Long Non-coding RNA-MicroRNA-mRNA Interactions in the Nucleus Accumbens Related to Morphine Addiction in Mice.Frontiers in psychiatry · 2022Article
- Metallothioneins and Megalin Expression Profiling in Premalignant and Malignant Oral Squamous Epithelial Lesions.Cancers · 2021Article
- The role of transthyretin in cell biology: impact on human pathophysiology.Cellular and molecular life sciences : CMLS · 2021Review
- Endocytic Protein Defects in the Neural Crest Cell Lineage and Its Pathway Are Associated with Congenital Heart Defects.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Donnai-Barrow syndrome, a genetic disorder associated to LRP2 (low-density lipoprotein receptor 2/megalin) mutations, is characterized by unexplained neurological symptoms and intellectual deficits. Megalin is a multifunctional endocytic clearance cell-surface receptor, mostly described in epithelial cells. This receptor is also expressed in the CNS, mainly in neurons, being involved in neurite outgrowth and neuroprotective mechanisms. Yet, the mechanisms involved in the regulation of megalin in the CNS are poorly understood. Using transthyretin knockout mice, a megalin ligand, we found that transthyretin positively regulates neuronal megalin levels in different CNS areas, particularly in the hippocampus. Transthyretin is even able to rescue megalin downregulation in transthyretin knockout hippocampal neuronal cultures, in a positive feedback mechanism via megalin. Importantly, transthyretin activates a regulated intracellular proteolysis mechanism of neuronal megalin, producing an intracellular domain, which is translocated to the nucleus, unveiling megalin C-terminal as a potential transcription factor, able to regulate gene expression. We unveil that neuronal megalin reduction affects physiological neuronal activity, leading to decreased neurite number, length and branching, and increasing neuronal susceptibility to a toxic insult. Finally, we unravel a new unexpected role of megalin in synaptic plasticity, by promoting the formation and maturation of dendritic spines, and contributing for the establishment of active synapses, both in
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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.