Journal
INTERNATIONAL JOURNAL OF NEUROSCIENCE
Volume 123, Issue 1, Pages 42-49Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/00207454.2012.724127
Keywords
A beta oligomer; neuronal survival; plasminogen activator inhibitor-1; synaptic plasticity
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Funding
- SNUH Research Fund [880-20110051]
- SNU College of Medicine [800-20110052]
- National Research Foundation of Korea, Republic of Korea [2008-314-E00179]
- National Research Foundation of Korea [2012R1A1A2020118, 2008-314-E00179] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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-beta 1 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) (A beta(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 A beta(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 A beta(1-42)-oligomer-induced neurotoxicity in rat primary cultured hippocampal neurons.
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