| RRC ID |
80040
|
| 著者 |
Lee J, Lee H, Lee H, Shin M, Shin MG, Seo J, Lee EJ, Park SA, Park S.
|
| タイトル |
ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells.
|
| ジャーナル |
Nat Commun
|
| Abstract |
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.
|
| 巻・号 |
14(1)
|
| ページ |
8463
|
| 公開日 |
2023-12-20
|
| DOI |
10.1038/s41467-023-44319-3
|
| PII |
10.1038/s41467-023-44319-3
|
| PMID |
38123547
|
| PMC |
PMC10733300
|
| MeSH |
Amyloid beta-Peptides / metabolism
Animals
Blood-Brain Barrier / metabolism
Brain / metabolism
Endothelial Cells / metabolism
Humans
Induced Pluripotent Stem Cells* / metabolism
Low Density Lipoprotein Receptor-Related Protein-1* / genetics
Low Density Lipoprotein Receptor-Related Protein-1* / metabolism
Mice
Receptors, LDL / genetics
Receptors, LDL / metabolism
|
| IF |
12.121
|
| リソース情報 |
| 実験動物マウス |
RBRC04495 |
