title: Novel role of transglutaminase 1 in corpora amylacea formation?
abstract: Corpora amylacea (CA) are both age and neurodegeneration-related spherical bodies, consisting of polymerized proteins, often thought to be involved in sequestration of hazardous products of cellular metabolism in brain. Although CA formation is associated with cellular stress, the process underlying their formation remains obscure. Transglutaminases (TGs) are stress associated enzymes that induce molecular cross-links, leading to polymerization of substrate proteins. TG expression and activity are elevated in Alzheimer's disease (AD) and Parkinson's disease (PD), and TG-catalyzed cross-links are present in their lesions. Considering the nature of CA, the aim of this study was to investigate the presence of TGs and TG cross-links in CA of healthy aging brain, AD and PD brain, using immunohistochemistry. We observed TG1 and TG cross-links in CA, together with typical cytoskeletal proteins. Furthermore, the presence of proteins associated with AD or PD pathogenesis was not altered in CA of disease brain compared to controls. We propose that TG1-catalyzed cross-linking and consequent polymerization of cytoskeletal and cytoskeleton-associated proteins may underlie CA formation.
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Center, Neuroscience Campus Amsterdam, The Netherlands. m.wilhelmus@vumc.nl
authors.forename: Micha M M
authors.initials: MM
authors.lastname: Wilhelmus
authors.forename: Robin
authors.initials: R
authors.lastname: Verhaar
authors.forename: John G J M
authors.initials: JG
authors.lastname: Bol
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: van Dam
authors.forename: Jeroen J M
authors.initials: JJ
authors.lastname: Hoozemans
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Rozemuller
authors.forename: Benjamin
authors.initials: B
authors.lastname: Drukarch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000201:enzymology* / Q000473:pathology; D010300:Parkinson Disease / Q000201:enzymology* / Q000473:pathology*; D013378:Substantia Nigra / Q000201:enzymology* / Q000473:pathology; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D011503:Transglutaminases; C105804:transglutaminase 1