ArticleMolecular neurodegeneration2012
Sorting nexin 12 interacts with BACE1 and regulates BACE1-mediated APP processing.
Article in Molecular neurodegeneration, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Analysis of the aging-related biomarker in a nonhuman primate model using multilayer omics.BMC genomics · 2024Article
- SNX17 Mediates Dendritic Spine Maturation via p140Cap.Molecular neurobiology · 2024Article
- Endocytosis and Alzheimer's disease.GeroScience · 2024Review
- Emerging Role of Sorting Nexin 17 in Human Health and Disease.Current protein & peptide science · 2024Review
- Deep learning-based identification of genetic variants: application to Alzheimer's disease classification.Briefings in bioinformatics · 2022Article
- Sorting Out Sorting Nexins Functions in the Nervous System in Health and Disease.Molecular neurobiology · 2021Review
- SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate.National science review · 2021Article
- Is It the Twilight of BACE1 Inhibitors?Current neuropharmacology · 2021Article
- Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer's disease.Molecular neurodegeneration · 2020Review
- Pulse Pressure: An Emerging Therapeutic Target for Dementia.Frontiers in neuroscience · 2020Article
- Cellular Trafficking of Amyloid Precursor Protein in Amyloidogenesis Physiological and Pathological Significance.Molecular neurobiology · 2019Review
- SNX8 Enhances Non-amyloidogenic APP Trafficking and Attenuates Aβ Accumulation and Memory Deficits in an AD Mouse.Frontiers in cellular neuroscience · 2019Article
- The Model of Aging Acceleration Network Reveals the Correlation of Alzheimer's Disease and Aging at System Level.BioMed research international · 2019Article
- Sorting nexin 3 mutation impairs development and neuronal function in Caenorhabditis elegans.Cellular and molecular life sciences : CMLS · 2018Article
- Overexpression of SNX3 Decreases Amyloid-β Peptide Production by Reducing Internalization of Amyloid Precursor Protein.Neuro-degenerative diseases · 2018Article
- The Retromer Complex and Sorting Nexins in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2018Review
- Physiological Functions of the β-Site Amyloid Precursor Protein Cleaving Enzyme 1 and 2.Frontiers in molecular neuroscience · 2017Review
- miR-98-5p Acts as a Target for Alzheimer's Disease by Regulating Aβ Production Through Modulating SNX6 Expression.Journal of molecular neuroscience : MN · 2016Article
- SNX15 Regulates Cell Surface Recycling of APP and Aβ Generation.Molecular neurobiology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundβ-site APP cleaving enzyme 1 (BACE1) cleaves β-amyloid precursor protein (APP) to initiate the production of β-amyloid (Aβ), the prime culprit in Alzheimer's disease (AD). Dysregulation of the intracellular trafficking of BACE1 may affect Aβ generation, contributing to AD pathology. In this study, we investigated whether BACE1 trafficking and BACE1-mediated APP processing/Aβ generation are affected by sorting nexin 12 (SNX12), a member of the sorting nexin (SNX) family that is involved in protein trafficking regulation.
resultsHerein, we find that SNX12 is widely expressed in brain tissues and is mainly localized in the early endosomes. Overexpression of SNX12 does not affect the steady-state levels of APP, BACE1 or γ-secretase components, but dramatically reduces the levels of Aβ, soluble APPβ and APP β-carboxyl terminal fragments. Downregulation of SNX12 has the opposite effects. Modulation of SNX12 levels does not affect γ-secretase activity or in vitro β-secretase activity. Further studies reveal that SNX12 interacts with BACE1 and downregulation of SNX12 accelerates BACE1 endocytosis and decreases steady-state level of cell surface BACE1. Finally, we find that the SNX12 protein level is dramatically decreased in the brain of AD patients as compared to that of controls.
conclusionThis study demonstrates that SNX12 can regulate the endocytosis of BACE1 through their interaction, thereby affecting β-processing of APP for Aβ production. The reduced level of SNX12 in AD brains suggests that an alteration of SNX12 may contribute to AD pathology. Therefore, inhibition of BACE1-mediated β-processing of APP by regulating SNX12 might serve as an alternative strategy in developing an AD intervention.
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