ArticleAlzheimer's research & therapy2017
Sorting nexin-4 regulates β-amyloid production by modulating β-site-activating cleavage enzyme-1.
Article in Alzheimer's research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 44 citations in OpenAlex.
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- Unraveling the Genetic Landscape of Neurological Disorders: Insights into Pathogenesis, Techniques for Variant Identification, and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Endocytosis and Alzheimer's disease.GeroScience · 2024Review
- BIN1 in the Pursuit of Ousting the Alzheimer's Reign: Impact on Amyloid and Tau Neuropathology.Neurotoxicity research · 2023Review
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- Study of molecular patterns associated with ferroptosis in Parkinson's disease and its immune signature.PloS one · 2023Article
- Characterization of gene expression patterns in mild cognitive impairment using a transcriptomics approach and neuroimaging endophenotypes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Rare variants and HLA haplotypes associated in patients with neuromyelitis optica spectrum disorders.Frontiers in immunology · 2022Article
- A brain proteomic signature of incipient Alzheimer's disease in youngScience advances · 2021Article
- Alzheimer's disease BIN1 coding variants increase intracellular Aβ levels by interfering with BACE1 recycling.The Journal of biological chemistry · 2021Article
- Sorting Out Sorting Nexins Functions in the Nervous System in Health and Disease.Molecular neurobiology · 2021Review
- SNX-PXA-RGS-PXC Subfamily of SNXs in the Regulation of Receptor-Mediated Signaling and Membrane Trafficking.International journal of molecular sciences · 2021Review
- Sorting Nexins in Protein Homeostasis.Cells · 2020Review
- The endosomal protein sorting nexin 4 is a synaptic protein.Scientific reports · 2020Article
- Wild mice with different social network sizes vary in brain gene expression.BMC genomics · 2020Article
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- Cross-Sectional Transcriptional Analysis of the Aging Murine Heart.Frontiers in molecular biosciences · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAmyloid precursor protein (APP) is cleaved by β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) to produce β-amyloid (Aβ), a critical pathogenic peptide in Alzheimer's disease (AD). Aβ generation can be affected by the intracellular trafficking of APP or its related secretases, which is thus important to understanding its pathological alterations. Although sorting nexin (SNX) family proteins regulate this trafficking, the relevance and role of sorting nexin-4 (SNX4) regarding AD has not been studied yet.
methodsIn this study, human brain tissue and APP/PS1 mouse brain tissue were used to check the disease relevance of SNX4. To investigate the role of SNX4 in AD pathogenesis, several experiments were done, such as coimmunoprecipitation, Western blotting, immunohistochemistry, and gradient fractionation.
resultsWe found that SNX4 protein levels changed in the brains of patients with AD and of AD model mice. Overexpression of SNX4 significantly increased the levels of BACE1 and Aβ. Downregulation of SNX4 had the opposite effect. SNX4 interacts with BACE1 and prevents BACE1 trafficking to the lysosomal degradation system, resulting in an increased half-life of BACE1 and increased production of Aβ.
conclusionsWe show that SNX4 regulates BACE1 trafficking. Our findings suggest novel therapeutic implications of modulating SNX4 to regulate BACE1-mediated β-processing of APP and subsequent Aβ generation.
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