Article abstract
Nature Cell Biology 11, 143 - 153 (2008)
Published online: 21 December 2008 | doi:10.1038/ncb1819
SRF and myocardin regulate LRP-mediated amyloid-
clearance in brain vascular cells
Robert D. Bell1, Rashid Deane1, Nienwen Chow2, Xiaochun Long3, Abhay Sagare1, Itender Singh1, Jeffrey W. Streb3, Huang Guo1,2, Anna Rubio2, William Van Nostrand4, Joseph M. Miano3,5 & Berislav V. Zlokovic1,5
Abstract
Amyloid 
-peptide (A) 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 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 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 cerebrovascular clearance and progression of AD.
- Center for Neurodegenerative and Vascular Brain Disorders, Arthur Kornberg Medical Research Building, University of Rochester School of Medicine & Dentistry, 601 Elmwood Avenue, Rochester, New York 14642, USA
- Socratech Research Laboratories, University of Rochester School of Medicine & Dentistry, 601 Elmwood Avenue, Rochester, New York 14642, USA.
- Aab Cardiovascular Research Institute, University of Rochester School of Medicine & Dentistry, 601 Elmwood Avenue, Rochester, New York 14642, USA
- Department of Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- J.M.M. and B.V.Z. were co-senior authors.
Correspondence to: Berislav V. Zlokovic1,5 e-mail: berislav_zlokovic@urmc.rochester.edu
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