Current Concepts of the Role of Striatal-Enriched Protein Tyrosine Phosphatase STEP in the Pathological and Neurodegenerative Processes in the Brain

Abstract—Striatal-enriched protein tyrosine phosphatase (STEP) is an intracellular protein involved in key signaling cascades of the nerve cell. By regulating the membrane localization of glutamate receptors and the activity of several signaling kinases, STEP can influence processes of neuroplasticity and synaptic function, and participate in the regulation of behavior, cognition, and memory. STEP can act as an intermediary between the brain neurotrophic, dopaminergic, and glutamatergic systems. Dysregulation of STEP expression and function is observed in several neurodegenerative and psychiatric disorders, as well as in aging and traumatic brain injuries. In Alzheimer’s and Parkinson’s diseases, as well as in fragile X syndrome, there is an increase in STEP activity and expression in the brains of patients and in animal models of these diseases. There is evidence of this phosphatase’s involvement in the mechanisms of depression, autism spectrum disorders, schizophrenia, and anxiety; however, different model systems and experimental conditions yield contradictory results. STEP plays a modulatory role in the nervous system response to traumatic brain injuries, ischemic stroke, epileptic seizures, and stress exposure. Due to STEP involvement in the pathogenesis of numerous nervous system disorders, this phosphatase has been actively studied over the past decade. In this review, we comprehensively examine the existing data on the role of STEP phosphatase in the functioning of CNS and in the mechanisms of disease development and the response of nerve cells to damaging influences.