title: FK506 reduces amyloid plaque burden and induces MMP-9 in AβPP/PS1 double transgenic mice.
abstract: Deposition of amyloid-β peptide (Aβ) and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Recently, calcineurin (CaN) has been reported as a potential modulator of memory function, synaptic plasticity, and neural degeneration in brains of AD animal models. In the present study, we examined the relationship between Aβ accumulations and CaN activity in brains of the AβPP/PS1 double transgenic mice. Treatment with FK506, a CaN inhibitor, significantly reduces Aβ burden and restores synaptic proteins (synaptophysin and postsynaptic density protein-95; PSD-95) while inducing matrix metallopeptidase-9 (MMP-9) expression in GFAP-positive astrocytes in the brain. These results suggest a role of FK506 and control of CaN activity in neuroprotection associated with Aβ deposition in AD.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyun-Seok
authors.initials: HS
authors.lastname: Hong
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Hwang
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Son
authors.forename: Yoon-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Minho
authors.initials: M
authors.lastname: Moon
authors.forename: Mook-Jung
authors.initials: MJ
authors.lastname: Inhee
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D005260:Female; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D058225:Plaque, Amyloid / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D020780:Matrix Metalloproteinase 9; D016559:Tacrolimus