SRF and myocardin regulate LRP-mediated amyloid-β clearance in brain vascular cells

被引：220

作者：

Bell, Robert D. ^{[1
]}

Deane, Rashid ^{[1
]}

Chow, Nienwen ^{[2
]}

Long, Xiaochun ^{[3
]}

Sagare, Abhay ^{[1
]}

Singh, Itender ^{[1
]}

Streb, Jeffrey W. ^{[3
]}

Guo, Huang ^{[1
,2
]}

Rubio, Anna ^{[2
]}

Van Nostrand, William ^{[4
]}

Miano, Joseph M. ^{[3
]}

Zlokovic, Berislav V. ^{[1
]}

机构：

[1] Univ Rochester, Sch Med & Dent, Ctr Neurodegenerat & Vasc Brain Disorders, Rochester, NY 14642 USA

[2] Univ Rochester, Sch Med & Dent, Socratech Res Labs, Rochester, NY 14642 USA

[3] Univ Rochester, Sch Med & Dent, Aab Cardiovasc Res Inst, Rochester, NY 14642 USA

[4] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA

来源：

NATURE CELL BIOLOGY | 2009年 / 11卷 / 02期

关键词：

SERUM RESPONSE FACTOR; ELEMENT-BINDING PROTEIN-2; ALZHEIMER-DISEASE; NEUROVASCULAR DYSFUNCTION; APOLIPOPROTEIN-E; IN-VITRO; PEPTIDE; SMOOTH; GENE; EXPRESSION;

D O I：

10.1038/ncb1819

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Amyloid beta-peptide (A beta) deposition in cerebral vessels contributes to cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD). Here, we report that in AD patients and two mouse models of AD, overexpression of serum response factor (SRF) and myocardin (MYOCD) in cerebral vascular smooth muscle cells (VSMCs) generates an A beta non-clearing VSMC phenotype through transactivation of sterol regulatory element binding protein-2, which downregulates low density lipoprotein receptor-related protein-1, a key A beta clearance receptor. Hypoxia stimulated SRF/MYOCD expression in human cerebral VSMCs and in animal models of AD. We suggest that SRF and MYOCD function as a transcriptional switch, controlling A beta cerebrovascular clearance and progression of AD.

引用

页码：143 / U83

页数：21

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