Regulation of post-ischemic inflammatory response: A novel function of the neuronal tyrosine phosphatase STEP.

Regulation of post-ischemic inflammatory response: A novel function of the neuronal tyrosine phosphatase STEP. Brain Behav Immun. 2021 Jan 07;: Authors: Rajagopal S, Yang C, DeMars KM, Poddar R, Candelario-Jalil E, Paul S Abstract The neuron-specific tyrosine phosphatase STEP is emerging as a key neuroprotectant against acute ischemic stroke. However, it remains unclear how STEP impacts the outcome of stroke. We find that the exacerbation of ischemic brain injury in STEP deficient mice involves an early onset and sustained activation of neuronal p38 mitogen activated protein kinase, a substrate of STEP. This leads to rapid increase in the expression of neuronal cyclooxygenase-2 and synthesis of prostaglandin E2, causing change in microglial morphology to an amoeboid activated state, activation of matrix metalloproteinase-9, cleavage of tight junction proteins and extravasation of IgG into the ischemic brain. Restoration of STEP signaling with intravenous administration of a STEP-derived peptide mimetic reduces the post-ischemic inflammatory response and attenuates brain injury. The findings identify a unique role of STEP in regulating post-ischemic neuroinflammation and further emphasizes the therapeutic potential of the STEP-mimetic in neurological disorders where inflammation contributes to brain damage. PMID: 33422638 [PubMed - as supplied by publisher]
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research