Blocking TrkB's Effectors Reveal Benefits of the Road Not Taken.

Blocking TrkB's Effectors Reveal Benefits of the Road Not Taken.
Epilepsy Curr. 2019 Sep 09;:1535759719872503
Authors: Danzer SC
Abstract
TrkB-Shc Signaling Protects Against Hippocampal Injury Following Status Epilepticus Huang YZ, He XP, Krishnamurthy K, McNamara JO. J Neurosci. 2019;39(23):4624-4630. doi:10.1523/JNEUROSCI.2939-18.2019. Epub March 29, 2019. PMID: 30926745 Temporal lobe epilepsy (TLE) is a common and commonly devastating form of human epilepsy for which only symptomatic therapy is available. One cause of TLE is an episode of de novo prolonged seizures (status epilepticus [SE]). Understanding the molecular signaling mechanisms by which SE transforms a brain from normal to epileptic may reveal novel targets for preventive and disease-modifying therapies. Status epilepticus-induced activation of the brain-derived neurotrophic factor receptor tyrosine kinase B (TrkB) is one signaling pathway by which SE induces TLE. Although activation of TrkB signaling promotes development of epilepsy in this context, it also reduces SE-induced neuronal death. This led us to hypothesize that distinct signaling pathways downstream of TrkB mediate the desirable (neuroprotective) and undesirable (epileptogenesis) consequences. We subsequently demonstrated that TrkB-mediated activation of phospholipase Cγ1 is required for epileptogenesis. Here, we tested the hypothesis that the TrkB-Shc-Akt signaling pathway mediates the neuroprotective co...

Source: Epilepsy Curr - September 8, 2019 Category: Neurology Authors: Danzer SC Tags: Epilepsy Curr Source Type: research