Heat shock protein-90-induced microglial clearance of exogenous amyloid-beta1-42 in rat hippocampus in vivo.
Alzheimer's disease is characterized by the accumulation of extracellular amyloid-beta (A beta) fibrils with microglia. In an in vitro microglial culture, we recently found that heat-shock protein-90 (Hsp90) enhanced the microglial phagocytosis and clearance of A beta (1-42) (A beta 42). In this study, we examined the microinjection of A beta 42 in the presence or absence of Hsp90 into the rat hippocampus in vivo. Intrahippocampal injection of A beta 42 alone induced microglial accumulation, and the amount of A beta 42 then gradually decreased. In addition, simultaneous injection with Hsp90 significantly reduced the amount of A beta 42 and increased the production of cytokines. These results suggest that Hsp90 may facilitate microglial A beta 42 clearance in rat brain in vivo.
Takata
Kazuyuki
K
Department of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Kitamura
Yoshihisa
Y
Tsuchiya
Daiju
D
Kawasaki
Toshiyuki
T
Taniguchi
Takashi
T
Shimohama
Shun
S
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D018841:HSP90 Heat-Shock Proteins / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008845:Microinjections; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D018841:HSP90 Heat-Shock Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)