title: Self-assembling nanofibers alter the processing of amyloid precursor protein in a transgenic mouse model of Alzheimer's disease.
abstract: BACKGROUND
  Alzheimer's disease (AD) is one of the most common dementia, which is not effectively cured to date. Amyloid-beta (Abeta) deposition cascade and disintegrity of brain extracellular matrix (ECM) scaffold attribute to the progress of AD. Thus, it maybe an effective way to treat AD by altering the processing of amyloid precursor protein (APP) and regaining the integrity of ECM. The peptide amphiphile (PA) with a laminin epitope isoleucine-lysine-valine-alanine-valine (IKVAV) (IKVAV-PA) can be trigged into ECM in vivo. In addition, IKVAV-PA could significantly improve cognitive impairment with remarkable increase of endoneurogensis in the hippocampus, as well as reduction of burden of amyloid plaque in the brain.
  
  
  METHODS
  We used heterozygous AbetaPPswe/PS1dE9 double transgenic mice as the animal model of AD. After 1 week of initial stereotaxic administration into bilateral hippocampus, the mice were subjected to the Morris Water Maze (MWM) test. At the end of MWM test, immunohistochemical staining, Western blot and real-time polymerase chain reaction (PCR) were performed in mice.
  
  
  RESULTS
  Here we showed that IKVAV-PA significantly improved cognitive impairment accompanying with reducing the burden of Abeta plaques, as well as the levels of soluble Abeta1-40 and Abeta1-42 in the cortex and hippocampus after 2 weeks of initial administration into bilateral hippocampus. Further examination demonstrated that IKVAV-PA also altered the processing of APP via inhibiting the gene expression of beta-secretase (BACE1), as well as improving the gene expression of insulin-degrading enzyme (IDE) and neprilysin (NEP).
  
  
  CONCLUSIONS
  Our data suggest that IKVAV-PA may serve as an alternative therapeutic intervention for treating the learning and memory losses in AD.
authors.forename: Hongna
authors.initials: H
authors.lastname: Yang
authors.forename: Hongling
authors.initials: H
authors.lastname: Yang
authors.forename: Zhaohong
authors.initials: Z
authors.lastname: Xie
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Bi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007339:Insulysin / Q000378:metabolism; D007797:Laminin / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057139:Nanofibers / Q000008:administration & dosage*; D015260:Neprilysin / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007797:Laminin; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C083321:isoleucyl-lysyl-valyl-alanyl-valine; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D015260:Neprilysin; D007339:Insulysin
keywords: Alzheimer’s disease,; Impaired cognition,; Processing of APP; Self-assembling nanofibers,