title: Neuroprotective effects of LMW and HMW FGF2 against amyloid beta toxicity in primary cultured hippocampal neurons.
abstract: Basic Fibroblast growth factor (FGF2) is important in development and maintenance of central nervous system function. Studies have demonstrated that low molecular weight (LMW) FGF2 is a neuroprotective factor against various insults in vivo and in vitro. In the present study we investigated the neuroprotective effects of high molecular weight (HMW) and LMW FGF2 against amyloid beta-induced neurotoxicity. The results showed that both LMW and HMW FGF2 attenuated the amyloid beta toxicity in the primary cultured hippocampal neurons as measured by WST and LDH release assay. Moreover, the analysis suggested that HMW FGF2 had stronger neuroprotective effect than LMW FGF2. We then demonstrated that LMW and HMW FGF2 activated the ERK and AKT signaling pathways in a similar way. Furthermore, using the ERK inhibitor and AKT inhibitor, we found that the AKT signaling but not ERK signaling pathway was required for the neuroprotective effects of FGF2. Taken together, these results showed the neuroprotective effects of different forms of FGF2 in an AD model and the mechanism underlying the neuroprotection.
authors.affiliation: Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhaojin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Elissavet
authors.initials: E
authors.lastname: Kardami
authors.affiliation: Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lohp@mail.nih.gov.
authors.forename: Y Peng
authors.initials: YP
authors.lastname: Loh
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism / Q000633:toxicity; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D020033:Protein Isoforms; D016222:Fibroblast Growth Factor 2; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Amyloid beta; HMW FGF2; Hippocampal neuron; LMW FGF2