ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells
© 2023. The Author(s)..
Brain endothelial LDL receptor-related protein 1 (LRP1) is involved in the clearance of Aβ peptides across the blood-brain barrier (BBB). Here we show that endothelial deficiency of ankyrin repeat and SAM domain containing 1 A (ANKS1A) reduces both the cell surface levels of LRP1 and the Aβ clearance across the BBB. Association of ANKS1A with the NPXY motifs of LRP1 facilitates the transport of LRP1 from the endoplasmic reticulum toward the cell surface. ANKS1A deficiency in an Alzheimer's disease mouse model results in exacerbated Aβ pathology followed by cognitive impairments. These deficits are reversible by gene therapy with brain endothelial-specific ANKS1A. In addition, human induced pluripotent stem cell-derived BBBs (iBBBs) were generated from endothelial cells lacking ANKS1A or carrying the rs6930932 variant. Those iBBBs exhibit both reduced cell surface LRP1 and impaired Aβ clearance. Thus, our findings demonstrate that ANKS1A regulates LRP1-mediated Aβ clearance across the BBB.
| Errataetall: |
ErratumIn: Nat Commun. 2024 Apr 9;15(1):3062. - PMID 38594263 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Nature communications - 14(2023), 1 vom: 20. Dez., Seite 8463 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lee, Jiyeon [VerfasserIn] |
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| Links: |
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| Themen: |
ANKS1A protein, human |
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| Anmerkungen: |
Date Completed 02.01.2024 Date Revised 12.04.2024 published: Electronic ErratumIn: Nat Commun. 2024 Apr 9;15(1):3062. - PMID 38594263 Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-44319-3 |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Brain endothelial LDL receptor-related protein 1 (LRP1) is involved in the clearance of Aβ peptides across the blood-brain barrier (BBB). Here we show that endothelial deficiency of ankyrin repeat and SAM domain containing 1 A (ANKS1A) reduces both the cell surface levels of LRP1 and the Aβ clearance across the BBB. Association of ANKS1A with the NPXY motifs of LRP1 facilitates the transport of LRP1 from the endoplasmic reticulum toward the cell surface. ANKS1A deficiency in an Alzheimer's disease mouse model results in exacerbated Aβ pathology followed by cognitive impairments. These deficits are reversible by gene therapy with brain endothelial-specific ANKS1A. In addition, human induced pluripotent stem cell-derived BBBs (iBBBs) were generated from endothelial cells lacking ANKS1A or carrying the rs6930932 variant. Those iBBBs exhibit both reduced cell surface LRP1 and impaired Aβ clearance. Thus, our findings demonstrate that ANKS1A regulates LRP1-mediated Aβ clearance across the BBB | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Low Density Lipoprotein Receptor-Related Protein-1 |2 NLM | |
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| 700 | 1 | |a Lee, Hyein |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Miram |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Min-Gi |e verfasserin |4 aut | |
| 700 | 1 | |a Seo, Jinsoo |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Eun Jeong |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Sun Ah |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Soochul |e verfasserin |4 aut | |
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