The role of endogenous tissue-type plasminogen activator in neuronal survival after ischemic stroke: friend or foe?

The role of endogenous tissue-type plasminogen activator in neuronal survival after ischemic stroke: friend or foe? Cell Mol Life Sci. 2019 Jan 17;: Authors: Zhu J, Wan Y, Xu H, Wu Y, Hu B, Jin H Abstract Endogenous protease tissue-type plasminogen activator (tPA) has highly efficient fibrinolytic activity and its recombinant variants alteplase and tenecteplase are established as highly effective thrombolytic drugs for ischemic stroke. Endogenous tPA is constituted of five functional domains through which it interacts with a variety of substrates, binding proteins and receptors, thus having enzymatic and cytokine-like effects to act on all cell types of the brain. In the past 2 decades, numerous studies have explored the clinical relevance of endogenous tPA in neurological diseases, especially in ischemic stroke. tPA is released from many cells within the brain parenchyma exposed to ischemia conditions in vitro and in vivo, which is believed to control neuronal fate. Some studies proved that tPA could induce blood-brain barrier disruption, neural excitotoxicity and inflammation, while others indicated that tPA also has anti-excitotoxic, neurotrophic and anti-apoptotic effects on neurons. Therefore, more work is needed to elucidate how tPA mediates such opposing functions that may amplify tPA from a therapeutic means into a key therapeutic target in endogenous neuroprotection after stroke. In this review, we summarize the biological ...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research