Involvement of the Urokinase Receptor and Its Endogenous Ligands in the Development of the Brain and the Formation of Cognitive Functions

Studies in recent years have shown that the urokinase receptor (uPAR) and its ligands – urokinase (uPA) and protein SRPX2 – play important roles in the processes underlying the formation and functioning of the brain. Human studies have demonstrated an interaction between a polymorphism of the uPAR gene and the development of autism. Patients with autism, incurable epilepsy, verbal dyspraxia, and perisylvian polymicrogyria show changes in uPAR expression. Studies using mice with knockout of the uPAR gene showed a tendency to develop epilepsy and impairments to behavioral reactions. Data have also been obtained on the involvement of uPAR ligands – uPA and protein SRPX2 – in the development of pathological brain states associated with autism, cognitive disorders, and speech disorders. The urokinase system has been shown to be able to regulate not only the rate of growth of vessels and nerve fibers by remodeling the matrix and activating neurotrophic and angiogenic factors, but also to function as a system of navigation molecules determining the direction of vessel and nerve growth in tissue regeneration processes. This article summarizes and analyzes results from recent studies of the role of uPAR and its endogenous ligands in the development of the brain and the formation of the cognitive functions.