Exp Cell Res 313(10): 2077-2087

GFAP and its role in Alexander Disease

^{School of Biological and Biomedical Sciences, The University, Durham DH1 3LE, UK}

^{Department of Neurobiology, Evelyn F. McKnight Brain Institute, Center for Glial Biology in Medicine, University of Alabama Birmingham, Birmingham, AL35294}

^{Columbia University, Department of Pathology and The Center for Neurobiology and Behavior, 630 W. 168th St., New York, NY 10032}

^{Waisman Center and Department of Comparative Biosciences, University of Wisconsin Madison, Madison, WI53705}

^{Author for correspondence:}ku.ca.mahrud@nalniuq.a.r, Tel: (44)- 191-3341331, Fax: (44)-191-3341201

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Abstract

Here we review how GFAP mutations cause Alexander disease. The current data suggest that a combination of events cause the disease. These include: i) the accumulation of GFAP and the formation of characteristic aggregates, called Rosenthal fibres, ii) the sequestration of the protein chaperones αB-crystallin and HSP27 into Rosenthal fibres, and iii) the activation of both Jnk and the stress response. These then set in motion events that lead to Alexander disease. We discuss parallels with other intermediate filament diseases and assess potential therapies as part of this review as well as emerging trends in disease diagnosis and other aspects concerning GFAP.

Keywords: Alexander disease, GFAP, chaperone, alphaB-crystallin, Jnk, MLK

Abstract

Footnotes

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