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Nat Cell Biol. 2009 Feb;11(2):143-53. doi: 10.1038/ncb1819. Epub 2008 Dec 21.

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

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  • 1Center 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.

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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PMID:
19098903
[PubMed - indexed for MEDLINE]
PMCID:
PMC2654279
Free PMC Article

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