ArticleProceedings of the National Academy of Sciences of the United States of America2006
LRRTM3 promotes processing of amyloid-precursor protein by BACE1 and is a positional candidate gene for late-onset Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 94 citations in OpenAlex.
- A decade of progress in understanding LRRTM and Slitrk synaptic cell-adhesion molecules.Molecules and cells · 2026Review
- Contribution of amyloid deposition from oligodendrocytes in a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2024Article
- siRNA drug delivery across the blood-brain barrier in Alzheimer's disease.Advanced drug delivery reviews · 2023Review
- Transcriptome-wide association study identifies novel candidate susceptibility genes for migraine.HGG advances · 2023Article
- LRRTM3 Genetic Variations, rs1925575, and rs1925608 Contributed to Autism Spectrum Disorder Trait Severity: An Observation in The Indian Probands.International journal of molecular and cellular medicine · 2023Article
- Amyloid precursor protein (APP) and amyloid β (Aβ) interact with cell adhesion molecules: Implications in Alzheimer's disease and normal physiology.Frontiers in cell and developmental biology · 2022Review
- A brain proteomic signature of incipient Alzheimer's disease in youngScience advances · 2021Article
- Emerging evidence implicating a role for neurexins in neurodegenerative and neuropsychiatric disorders.Open biology · 2021Review
- Glypicans and Heparan Sulfate in Synaptic Development, Neural Plasticity, and Neurological Disorders.Frontiers in neural circuits · 2021Review
- Targeted sequencing of the LRRTM gene family in suicide attempters with bipolar disorder.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2020Article
- Synaptic Organizers in Alzheimer's Disease: A Classification Based on Amyloid-β Sensitivity.Frontiers in cellular neuroscience · 2020Review
- Modeling the Kinetics of Lipid-Nanoparticle- Mediated Delivery of Multiple siRNAs to Evaluate the Effect on Competition for Ago2.Molecular therapy. Nucleic acids · 2019Article
- Leucine-rich repeat-containing synaptic adhesion molecules as organizers of synaptic specificity and diversity.Experimental & molecular medicine · 2018Review
- Enhanced synaptic plasticity and spatial memory in female but not male FLRT2-haplodeficient mice.Scientific reports · 2018Article
- Using High-Throughput Animal or Cell-Based Models to Functionally Characterize GWAS Signals.Current genetic medicine reports · 2018Review
- Gene expression, methylation and neuropathology correlations at progressive supranuclear palsy risk loci.Acta neuropathologica · 2016Article
- Lingo-1: a novel target in therapy for Alzheimer's disease?Neural regeneration research · 2016Article
- Synaptic Cell Adhesion Molecules in Alzheimer's Disease.Neural plasticity · 2016Review
- Genome-wide miR-155 and miR-802 target gene identification in the hippocampus of Ts65Dn Down syndrome mouse model by miRNA sponges.BMC genomics · 2015Article
- New functions for alpha-catenins in health and disease: from cancer to heart regeneration.Cell and tissue research · 2015Review
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Authors and funding
29 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rare familial forms of Alzheimer's disease (AD) are thought to be caused by elevated proteolytic production of the Abeta42 peptide from the beta-amyloid-precursor protein (APP). Although the pathogenesis of the more common late-onset AD (LOAD) is not understood, BACE1, the protease that cleaves APP to generate the N terminus of Abeta42, is more active in patients with LOAD, suggesting that increased amyloid production processing might also contribute to the sporadic disease. Using high-throughput siRNA screening technology, we assessed 15,200 genes for their role in Abeta42 secretion and identified leucine-rich repeat transmembrane 3 (LRRTM3) as a neuronal gene that promotes APP processing by BACE1. siRNAs targeting LRRTM3 inhibit the secretion of Abeta40, Abeta42, and sAPPbeta, the N-terminal APP fragment produced by BACE1 cleavage, from cultured cells and primary neurons by up to 60%, whereas overexpression increases Abeta secretion. LRRTM3 is expressed nearly exclusively in the nervous system, including regions affected during AD, such as the dentate gyrus. Furthermore, LRRTM3 maps to a region of chromosome 10 linked to both LOAD and elevated plasma Abeta42, and is structurally similar to a family of neuronal receptors that includes the NOGO receptor, an inhibitor of neuronal regeneration and APP processing. Thus, LRRTM3 is a functional and positional candidate gene for AD, and, given its receptor-like structure and restricted expression, a potential therapeutic target.
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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.