title: Plasminogen activator inhibitor-1 promotes synaptogenesis and protects against aβ(1-42)-induced neurotoxicity in primary cultured hippocampal neurons.
abstract: Plasminogen activator inhibitor-1 (PAI-1) is a soluble factor that is released from astrocytes, the most abundant type of glial cell in the brain. PAI-1 was initially identified as inhibiting two types of plasminogen activators, that is, tissue-type plasminogen and urokinase activators that are known to lead to the proteolytic degradation of the extracellular matrix. Recently, PAI-1 was reported to mediate the neuroprotective activity of transforming growth factor-β1 against N-methyl-D-aspartate receptor-mediated excitotoxicity and to be involved in angiogenesis following ischemic stroke, independently of the effects via the inhibition of tissue-type plasminogen and urokinase-type plasminogen activators. In this study, we examined whether PAI-1 influences synaptogenesis and neurotoxicity induced by amyloid beta peptide(1-42) (Aß(1-42)) in rat primary hippocampal neurons. Using immunostaining, treatment with PAI-1 for 24 h was found to significantly upregulate synaptophysin, postsynaptic density-95, and the polysialylated form of neural cell adhesion molecule, compared to treatment with vehicle alone. In addition, PAI-1 has neuroprotective effects against Aβ(1-42)-induced cytotoxicity in rat primary cultured hippocampal neurons. Taken together, our results suggest that PAI-1 has therapeutic potential in Alzheimer's disease by promoting synaptogenesis and by demonstrating neuroprotective effects against Aβ(1-42)-oligomer-induced neurotoxicity in rat primary cultured hippocampal neurons.
authors.affiliation: Department of Biomedical Sciences, Seoul National University Graduate School, Daehakro 103, Jongro-gu, Seoul, Korea.
authors.forename: Harim
authors.initials: H
authors.lastname: Cho
authors.forename: Yuyoung
authors.initials: Y
authors.lastname: Joo
authors.forename: Seonghan
authors.initials: S
authors.lastname: Kim
authors.forename: Ran-Sook
authors.initials: RS
authors.lastname: Woo
authors.forename: Sang Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D005333:Fetus; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase; D008565:Membrane Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D010446:Peptide Fragments / Q000633:toxicity*; D017395:Plasminogen Activator Inhibitor 1 / Q000494:pharmacology*; D051381:Rats; D012794:Sialic Acids / Q000378:metabolism; D013569:Synapses / Q000187:drug effects*; D016708:Synaptophysin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D039842:Neural Cell Adhesion Molecule L1; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D012794:Sialic Acids; D016708:Synaptophysin; C075222:amyloid beta-protein (1-42); C103469:polysialyl neural cell adhesion molecule; D007770:L-Lactate Dehydrogenase