SRF and Myocardin Regulate LRP-mediated Amyloid-beta Clearance in Brain Vascular Cells

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2008 Dec 23

PMID 19098903

Citations 136

Authors

Robert D Bell

Rashid Deane

Nienwen Chow

Xiaochun Long

Abhay Sagare

Itender Singh

Jeffrey W Streb

Huang Guo

Anna Rubio

William Van Nostrand

Joseph M Miano

Berislav V Zlokovic

Affiliations

Soon will be listed here.

Abstract

Amyloid beta-peptide (Abeta) 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 Abeta non-clearing VSMC phenotype through transactivation of sterol regulatory element binding protein-2, which downregulates low density lipoprotein receptor-related protein-1, a key Abeta 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 Abeta cerebrovascular clearance and progression of AD.

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