Role of high mobility group protein-1 (HMG1) in amyloid-beta homeostasis.
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.
Takata
Kazuyuki
K
Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
Kitamura
Yoshihisa
Y
Kakimura
Jun-ichi
J
Shibagaki
Keiichi
K
Tsuchiya
Daiju
D
Taniguchi
Takashi
T
Smith
Mark A
MA
Perry
George
G
Shimohama
Shun
S
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
D016229:Amyloid beta-Peptides; D024243:HMGB1 Protein; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)