title: Protective Effects of Colivelin Against Alzheimer's Disease in a PDAPP Mouse Model.
abstract: BACKGROUND
  Alzheimer's disease (AD) is characterized with progressive memory loss and severe cognitive impairments, which affect everyday life and human health in the elderly. It is required that an effective and safe protective reagent against AD should be developed. It has been reported that humanin (HN) exerts neuroprotective effects against AD. In this study, we investigated the effect of a novel and more effective HN derivative, Colivelin (CLN) on AD.
  
  
  METHODS
  PDAPP(V717I) transgenic AD model mice (derived from parental C57/BL6 mice) were used in our study as AD model. Morris water maze test was used to test the memory impairment of AD mice and the levels of Aβ40 and Aβ42 were determined by an Elisa assay. We used an Immunohistochemistry and Immunofluorescence staining method to check the GFAP and MAP2 positive cells, and TUNEL to assess the apoptotic cells. Western blot assay was used to check the expression and phosphorylation level of p38.
  
  
  RESULTS
  We found that CLN improved the memory impairment induced by AD and reduced the deposit of Aβ40 and Aβ42. CLN also inhibited cell apoptosis and activation of caspase 3 in brain tissues of AD mice. Inflammation in AD mice was alleviated by CLN treatment, including the accumulation of GFAP positive cells and the inflammatory cytokines. With both structure of AGA-HNG and ANDF, CLN exhibited significantly stronger effects than synchronously administration of AGA-HNG and ADNF, suggesting CLN as a novel potential effective therapeutic reagent for AD patients. Finally, we found that CLN inhibited phosphorylation of p38 in AD mice and p38 inhibitor, SB203580 weakened the therapeutic effect of CLN.
  
  
  CONCLUSIONS
  CLN effectively improved the memory dysfunction in PDAPP mice, and our data suggests CLN as a novel and effective reagent which may have great potentials in AD therapy.
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
authors.forename: Kai
authors.initials: K
authors.lastname: Yin
authors.forename: ZhiQiang
authors.initials: Z
authors.lastname: Guo
authors.forename: ZhiQiang
authors.initials: Z
authors.lastname: Zhang
authors.forename: LiPin
authors.initials: L
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.forename: YuanMin
authors.initials: Y
authors.lastname: Li
authors.forename: YaXuan
authors.initials: Y
authors.lastname: Wei
authors.forename: XueFeng
authors.initials: X
authors.lastname: Fu
authors.forename: XiangQun
authors.initials: X
authors.lastname: Shi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C508523:Colivelin; D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D048051:p38 Mitogen-Activated Protein Kinases