title: Role of high mobility group protein-1 (HMG1) in amyloid-beta homeostasis.
abstract: In Alzheimer's disease (AD), fibrillar amyloid-beta (Abeta) peptides form senile plaques associated with activated microglia. Recent studies have indicated that microglial Abeta clearance is facilitated by several activators such as transforming growth factor-beta1 (TGF-beta1). The relationship between microglia and Abeta formation and deposition is still unclear. In the present study, high mobility group protein-1 (HMG1) inhibited the microglial uptake of Abeta (1-42) in the presence and absence of TGF-beta1. In addition, HMG1 bound to Abeta (1-42) and stabilized the oligomerization. In AD brains, protein levels of HMG1 were significantly increased in both the cytosolic and particulate fractions, and HMG1 and Abeta were colocalized in senile plaques associated with microglia. These results suggest that HMG1 may regulate the homeostasis of extracellular Abeta (1-42) and Abeta oligomerization.
authors.affiliation: Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takata
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kakimura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Shibagaki
authors.forename: Daiju
authors.initials: D
authors.lastname: Tsuchiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D024243:HMGB1 Protein / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D017628:Microglia / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D010587:Phagocytosis; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D024243:HMGB1 Protein; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)