PP2A and tau – novel treatment targets in ischemic stroke and poststroke epilepsy

Project: Research

Project Description

Ischemic stroke is a common neurological condition that often results in debilitating lifelong consequences. One of the most severe, yet understudied, effects of stroke is the development of epilepsy. There is currently no intervention known to prevent the long-term neurological consequences of stroke, including epilepsy. The hyperphosphorylation of tau is implicated in a number of neurodegenerative diseases, like traumatic brain injury, Alzheimers, Parkinsons and epilepsy. Protein phosphatase 2A (PP2A) is the major tau phosphatase in the brain (i.e., it dephosphorylates tau). We have previously found that PP2A is downregulated in brain injury and epilepsy, and that treatment with sodium selenate (i.e., a potent PP2A agonist) decreases tau phosphorylation, improves brain injury outcomes (reduced brain dmage, improve congnition and improve mobility), an. prevents the the development of epilepsy. We now have exciting preliminary data showing that PP2A is decreased and tau is hyperphosphorylated in a rat model of ischemic stroke. Based on these promising results, this project will now test the hypotheses that PP2A and hyperphosphorylated tau contribute to the brain damage and functional consequences (e.g., mobility impariments, chronic pain, anxiety, social abnormalities, depression, learning and memory deficits, epilepsy) after stroke, and that treatment with sodium selenate can prevent these consequences. Sodium selenate treatment is already in clinical trials in other neurological conditions, thus this project has the strong potential to impact the medical management of stroke patients in the foreseeable future.
Short titleSodium selenate – a novel treatment for stroke and posttroke epilepsy
StatusActive
Effective start/end date1/11/1931/10/21

Keywords

  • stroke
  • epilepsy
  • tau
  • PP2A
  • pos-stroke epilepsy
  • beahviour
  • cognition
  • mobility
  • drug resistant
  • sodium selenate