title: Impacts of tissue-type plasminogen activator (tPA) on neuronal survival.
abstract: Tissue-type plasminogen activator (tPA) a serine protease is constituted of five functional domains through which it interacts with different substrates, binding proteins, and receptors. In the last years, great interest has been given to the clinical relevance of targeting tPA in different diseases of the central nervous system, in particular stroke. Among its reported functions in the central nervous system, tPA displays both neurotrophic and neurotoxic effects. How can the protease mediate such opposite functions remain unclear but several hypotheses have been proposed. These include an influence of the degree of maturity and/or the type of neurons, of the level of tPA, of its origin (endogenous or exogenous) or of its form (single chain tPA versus two chain tPA). In this review, we will provide a synthetic snapshot of our current knowledge regarding the natural history of tPA and discuss how it sustains its pleiotropic functions with focus on excitotoxic/ischemic neuronal death and neuronal survival.
authors.affiliation: INSERM, UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen-Normandie Caen, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chevilley
authors.affiliation: INSERM, UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen-Normandie Caen, France.
authors.forename: Flavie
authors.initials: F
authors.lastname: Lesept
authors.affiliation: INSERM, UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen-Normandie Caen, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lenoir
authors.affiliation: INSERM, UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen-Normandie Caen, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Ali
authors.affiliation: INSERM, UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen-Normandie Caen, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Parcq
authors.affiliation: INSERM, UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen-Normandie Caen, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
keywords: NMDA receptors; apoptosis; differential effects; excitotoxicity; tissue-type plasminogen activator