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Alexander Disease (alexander + disease)
Selected AbstractsAlexander disease and megalencephalic leukoencephalopathy with subcortical cysts: Leukodystrophies arising from astrocyte dysfunctionDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2006J. Rafael Gorospe [source] GFAP: Functional implications gleaned from studies of genetically engineered miceGLIA, Issue 1 2003Albee Messing Abstract GFAP is the major intermediate filament of mature astrocytes, and its relatively specific expression in these cells suggests an important function. To study the role of the GFAP gene, mice have been created carrying null alleles (no protein), modified alleles (altered protein), or added wild type alleles (elevated protein). Surprisingly, absence of GFAP has relatively subtle effects on development. On the other hand, over-expression can be lethal, and led to the discovery that GFAP coding mutations are responsible for most cases of Alexander disease, a devastating neurodegenerative disorder. Here we review what the various GFAP mouse models reveal about GFAP and astrocyte function. GLIA 43:87,90, 2003. © 2003 Wiley-Liss, Inc. [source] Novel GFAP mutation in patient with adult-onset Alexander disease presenting with spastic ataxia,MOVEMENT DISORDERS, Issue 9 2009Hiroyuki Kaneko MMed [source] Ser-59 is the major phosphorylation site in ,B-crystallin accumulated in the brains of patients with Alexander's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 3 2001Kanefusa Kato The phosphorylation state of ,B-crystallin accumulated in the brains of two patients with Alexander's disease (one infantile and one juvenile type) was determined by means of SDS-PAGE or isoelectric focusing of soluble and insoluble fractions of brain extracts and subsequent western blot analysis with specific antibodies against ,B-crystallin and each of three phosphorylated serine residues. The level of mammalian small heat shock protein of 25,28 kDa (Hsp27) in the same fraction was also estimated by western blot analysis. The majority of ,B-crystallin was detected in the insoluble fraction of brain homogenates and phosphorylation was preferentially observed at Ser-59 in both cases. A significant level of phosphorylation at Ser-45 but not Ser-19 was also detected. Hsp27 was found at considerable levels in the insoluble fractions. ,B-crystallin and phosphorylated forms were detected in the cerebrospinal fluid of patient with the juvenile type. ,B-crystallin and phosphorylated forms were also detectable at considerable levels in the insoluble fraction of brain homogenates from patients with Alzheimer's disease and aged controls. The phosphorylation site was mostly at Ser-59 in all cases. Immunohistochemically, ,B-crystallin was stained in Rosenthal fibers in brains of patients with Alexander's disease and their peripheral portions were immunostained with antibodies recognizing phosphorylated Ser-59. These results indicate that the major phosphorylation site in ,B-crystallin in brains of patients with Alexander's disease or Alzheimer's disease as well as in aged controls is Ser-59. [source] Small heat shock proteins, the cytoskeleton, and inclusion body formationNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2000M. W. Head Since first being implicated in central nervous system disease 10 years ago, much has been learned concerning the regulation and function of the small heat shock protein ,B-crystallin. Neuropathological, cellular and molecular studies all now point to a functional relationship between ,B-crystallin and intermediate filaments. ,B-crystallin accumulation marks reactive astrocytes in general in a wide variety of disorders and specifically intermediate filament-based glial inclusion bodies such as Rosenthal fibres found in astrocytes in Alexander's disease. In vitro, ,B-crystallin expression suppresses intermediate filament aggregation and can prevent or reverse experimentally induced glial inclusion body formation. Conversely, dysregulation of glial fibrillary acidic protein expression in vivo results in Rosenthal fibre formation and upregulation of endogenous ,B-crystallin expression. These data and those from studies recently carried out on other tissues strongly suggest that one function of this small heat shock protein is to modulate intermediate filament organization under conditions of physiological stress and neurodegenerative disease. [source] | |||||||||||||