Table of Contents
Cardiovascular Psychiatry and Neurology
Volume 2010, Article ID 687067, 14 pages
http://dx.doi.org/10.1155/2010/687067
Review Article

Targeting S100B in Cerebral Ischemia and in Alzheimer's Disease

1Department of Biomedical Sciences, Saitama Medical Center and University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan
2Department of Pathology, Saitama Medical Center and University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan
3Department of Biomedical Sciences, Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA
4Department of Neurosurgery, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA
5Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA

Received 31 March 2010; Revised 25 June 2010; Accepted 20 July 2010

Academic Editor: Rosario Donato

Copyright © 2010 Takashi Mori et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

S100B is an EF-hand calcium-binding protein that exerts both intracellular and extracellular effects on a variety of cellular processes. The protein is predominantly expressed in the central nervous system by astrocytes, both physiologically and during the course of neurological disease. In the healthy adult brain and during development, constitutive S100B expression acts as a trophic factor to drive neurite extension and to referee neuroplasticity. Yet, when induced during central nervous system disease, the protein can take on maladaptive roles and thereby exacerbate brain pathology. Based on genetic and pharmacological lines of evidence, we consider such deleterious roles of S100B in two common brain pathologies: ischemic stroke and Alzheimer's disease (AD). In rodent models of ischemic brain damage, S100B is induced early on during the subacute phase, where it exacerbates gliosis and delayed infarct expansion and thereby worsens functional recovery. In mouse models of AD, S100B drives brain inflammation and gliosis that accelerate cerebral amyloidosis. Pharmacological inhibition of S100B synthesis mitigates hallmark pathologies of both brain diseases, opening the door for translational approaches to treat these devastating neurological disorders.