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Int J Neurosci. 2013 Jan;123(1):42-9. doi: 10.3109/00207454.2012.724127. Epub 2012 Sep 27.

Plasminogen activator inhibitor-1 promotes synaptogenesis and protects against aβ(1-42)-induced neurotoxicity in primary cultured hippocampal neurons.

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1
Department of Biomedical Sciences, Seoul National University Graduate School, Daehakro 103, Jongro-gu, Seoul, Korea.

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.

PMID:
22937735
DOI:
10.3109/00207454.2012.724127
[Indexed for MEDLINE]
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