Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease

2005 ◽  
Vol 57 (3) ◽  
pp. 310-326 ◽  
Author(s):  
Rong Li ◽  
Anne B. Johnson ◽  
Gajja Salomons ◽  
James E. Goldman ◽  
Sakkubai Naidu ◽  
...  
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Alexander Disease ◽  
Acidic Protein ◽  
Protein Mutations

scholarly journals Glial fibrillary acidic protein exhibits altered turnover kinetics in a mouse model of Alexander disease

2017 ◽  
Vol 292 (14) ◽  
pp. 5814-5824 ◽  
Author(s):  
Laura R. Moody ◽  
Gregory A. Barrett-Wilt ◽  
Michael R. Sussman ◽  
Albee Messing
Keyword(s):  
Mouse Model ◽  
Glial Fibrillary Acidic Protein ◽  
Alexander Disease ◽  
Acidic Protein

scholarly journals Refining the concept of GFAP toxicity in Alexander disease

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Albee Messing
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glial Fibrillary Acidic Protein ◽  
Intermediate Filament ◽  
Alexander Disease ◽  
Acidic Protein ◽  
Sequence Variants ◽  
Main Body ◽  
Gain Of Function ◽  
The Central Nervous System

Abstract Background Alexander disease is caused by dominantly acting mutations in glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes in the central nervous system. Main body In addition to the sequence variants that represent the origin of disease, GFAP accumulation also takes place, together leading to a gain-of-function that has sometimes been referred to as “GFAP toxicity.” Whether the nature of GFAP toxicity in patients, who have mixtures of both mutant and normal protein, is the same as that produced by simple GFAP excess, is not yet clear. Conclusion The implications of these questions for the design of effective treatments are discussed.

scholarly journals Plectin Regulates the Organization of Glial Fibrillary Acidic Protein in Alexander Disease

2006 ◽  
Vol 168 (3) ◽  
pp. 888-897 ◽  
Author(s):  
Rujin Tian ◽  
Martin Gregor ◽  
Gerhard Wiche ◽  
James E. Goldman
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Alexander Disease ◽  
Acidic Protein

Juvenile Alexander disease with a novel mutation in glial fibrillary acidic protein gene

Neurology ◽  
2002 ◽  
Vol 58 (10) ◽  
pp. 1541-1543 ◽  
Author(s):  
Y. Sawaishi ◽  
T. Yano ◽  
I. Takaku ◽  
G. Takada
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Protein Gene ◽  
Novel Mutation ◽  
Alexander Disease ◽  
Acidic Protein

Adult onset Alexander disease with a novel variant (S398F) in the glial fibrillary acidic protein gene

2009 ◽  
Vol 49 (6) ◽  
pp. 358-363 ◽  
Author(s):  
Yoshimasa Sueda ◽  
Tetsuya Takahashi ◽  
Kazuhide Ochi ◽  
Toshiho Ohtsuki ◽  
Michito Namekawa ◽  
...  
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Protein Gene ◽  
Alexander Disease ◽  
Acidic Protein ◽  
Adult Onset ◽  
Novel Variant

scholarly journals Glial Fibrillary Acidic Protein Filaments Can Tolerate the Incorporation of Assembly-compromised GFAP-δ, but with Consequences for Filament Organization and αB-Crystallin Association

2008 ◽  
Vol 19 (10) ◽  
pp. 4521-4533 ◽  
Author(s):  
Ming-Der Perng ◽  
Shu-Fang Wen ◽  
Terry Gibbon ◽  
Jinte Middeldorp ◽  
Jacqueline Sluijs ◽  
...  
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Self Assembly ◽  
Fluorescent Protein ◽  
Physiological Role ◽  
Alexander Disease ◽  
Acidic Protein ◽  
Transfected Cells ◽  
Human Spinal Cord ◽  
Αb Crystallin

The glial fibrillary acidic protein (GFAP) gene is alternatively spliced to give GFAP-α, the most abundant isoform, and seven other differentially expressed transcripts including GFAP-δ. GFAP-δ has an altered C-terminal domain that renders it incapable of self-assembly in vitro. When titrated with GFAP-α, assembly was restored providing GFAP-δ levels were kept low (∼10%). In a range of immortalized and transformed astrocyte derived cell lines and human spinal cord, we show that GFAP-δ is naturally part of the endogenous intermediate filaments, although levels were low (∼10%). This suggests that GFAP filaments can naturally accommodate a small proportion of assembly-compromised partners. Indeed, two other assembly-compromised GFAP constructs, namely enhanced green fluorescent protein (eGFP)-tagged GFAP and the Alexander disease–causing GFAP mutant, R416W GFAP both showed similar in vitro assembly characteristics to GFAP-δ and could also be incorporated into endogenous filament networks in transfected cells, providing expression levels were kept low. Another common feature was the increased association of αB-crystallin with the intermediate filament fraction of transfected cells. These studies suggest that the major physiological role of the assembly-compromised GFAP-δ splice variant is as a modulator of the GFAP filament surface, effecting changes in both protein– and filament–filament associations as well as Jnk phosphorylation.

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