How PTEN keep neurons alive after stroke and injury

Seong-Seng Tan, Ley-Hian Low, Ulrich Putz, Choo-Peng Goh and Jason Howitt
Division of Brain Development and Regeneration
Florey Neuroscience Institute, The University of Melbourne, Australia


How does the brain defend itself from cell death following injury? Are there intrinsic mechanisms that protect neurons during critical periods of ischemic and metabolic stress? If yes, what are these mechanisms and why are they inefficient for keeping neurons alive following ischemia and injury?

In this presentation, I will outline key discoveries from our laboratory demonstrating that Ndfip1-mediated regulation of PTEN is a powerful and endogenous mechanism for increasing neuron survival following injury. PTEN is a major tumour suppressor shown to control cell survival and cell growth. Loss of PTEN, or PTEN mutation, is strongly correlated with poor cancer prognosis. Ndfip1 is a key mover of PTEN trafficking following PTEN ubiquination. We found that following stress, Ndfip1 is strongly increased in neurons. This step is required for PTEN to be ubiquitinated and trafficked into the neuron nucleus, resulting in increase phosphorylated Akt for neuron survival. In addition, Ndfip1 is required for PTEN to be exported out of cells inside exosomes. Thus by moving PTEN away from the cytoplasm, a cancer cell-survival pathway is activated in neurons.