title: No significant effect of 7,8-dihydroxyflavone on APP processing and Alzheimer-associated phenotypes.
abstract: It is reported that 7,8-dihydroxyflavone (DHF), a TrkB agonist, has beneficial effects on neuronal excitotoxicity, stroke, and Parkinson disease in animal models by enhancing axon regeneration, muscle reinnervation and neuromuscular transmission. The effect of DHF on AD neuropathology remains not well defined. In this study we examined whether DHF affects APP processing and cognitive functions in vitro and in vivo. We found that DHF had no significant effect on amyloid β precursor protein (APP), BACE1 and amyloid β protein (Aβ). DHF had little effect on APP processing in cell cultures. DHF treatment did not reduce the deposition of Aβ to form neuritic plaques in the brain of AD model mice APP23/PS45. Furthermore, DHF did not alleviate learning and memory impairments in the AD model mice. Our study suggest that further extensive and careful studies are warranted for considering DHF as a new therapeutic agent for reducing amyloid pathology and alleviating cognitive deficits for AD treatment.
authors.forename: Weitao
authors.initials: W
authors.lastname: Zhou
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Li
authors.forename: Daochao
authors.initials: D
authors.lastname: Huang
authors.forename: Weihui
authors.initials: W
authors.lastname: Zhou
authors.forename: Tingyu
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada; Fax: 604-822-7756; or Children's Hospital of Chongqing Medical University, Chongqing 400014, China. weihong@mail.ubc.ca.
authors.forename: Weihong
authors.initials: W
authors.lastname: Song
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D047309:Flavones / Q000627:therapeutic use*; D057809:HEK293 Cells; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: C485383:6,7-dihydroxyflavone; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D014150:Antipsychotic Agents; D047309:Flavones; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D012333:RNA, Messenger; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)