title: Synemin is expressed in reactive astrocytes and Rosenthal fibers in Alexander disease.
abstract: Alexander disease (AxD) is a neurodegenerative disorder with prominent white matter degeneration and the presence of Rosenthal fibers containing aggregates of glial fibrillary acidic protein (GFAP), and small stress proteins HSP27 and αB-crystallin, and widespread reactive gliosis. AxD is caused by mutations in GFAP, the main astrocyte intermediate filament protein. We previously showed that intermediate filament protein synemin is upregulated in reactive astrocytes after neurotrauma. Here, we examined immunohistochemically the presence of synemin in reactive astrocytes and Rosenthal fibers in two patients with AxD. There was an abundance of GFAP-positive Rosenthal fibers and widespread reactive gliosis in the white matter and subpial regions. Many of the GFAP-positive reactive astrocytes were positive for synemin, and synemin was also present in Rosenthal fibers. We show that synemin is expressed in reactive astrocytes in AxD, and is also present in Rosenthal fibers. The potential role of synemin in AxD pathogenesis remains to be investigated.
authors.affiliation: Department of Clinical Neuroscience and Rehabilitation, Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Tulen
authors.initials: T
authors.lastname: Pekny
authors.forename: Maryam
authors.initials: M
authors.lastname: Faiz
authors.forename: Ulrika
authors.initials: U
authors.lastname: Wilhelmsson
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Curtis
authors.forename: Radoslav
authors.initials: R
authors.lastname: Matej
authors.forename: Omar
authors.initials: O
authors.lastname: Skalli
authors.forename: Milos
authors.initials: M
authors.lastname: Pekny
mesh_terms: D000293:Adolescent; D038261:Alexander Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002648:Child; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D017354:Point Mutation; D014018:Tissue Distribution
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C430456:desmuslin
keywords: Alexander disease; Astrocytes; GFAP; intermediate filaments; neurodegenerative diseases