Diets involved in PPAR and PI3K/AKT/PTEN pathway may contribute to neuroprotection in a traumatic brain injury

Abstract

Traumatic encephalopathy has emerged as a significant public health problem. It is believed that traumatic encephalopathy is caused by exposure to repetitive brain trauma prior to the initial symptoms of neurodegenerative disease. Therefore, prevention is important for the disease. The PI3K/AKT/PTEN (phosphoinositide-3 kinase/AKT/phosphatase and tensin homologue deleted on chromosome 10) pathway has been shown to play a pivotal role in neuroprotection, enhancing cell survival by stimulating cell proliferation and inhibiting apoptosis. PTEN negatively regulates the PI3K/AKT pathways through its lipid phosphatase activity. Although PTEN has been discovered as a tumor suppressor, PTEN is also involved in several other diseases, including diabetes and Alzheimer’s disease. Dietary fish oil rich in polyunsaturated fatty acids may induce the PTEN expression by activation of peroxisome proliferator-activated receptor. Supplementation of these natural compounds may provide a new therapeutic approach to the brain disorder. We review recent studies on the features of several diets and the signaling pathways involved in traumatic encephalopathy.

Exogenous progesterone is neuroprotective following injury to the male zebra finch brain

“…The PI3K/Akt signaling pathway is the main cell survival and growth signal transduction pathway involved after cerebral damage (Kitagishi and Matsuda, ; Marin et al, ; Matsuda et al, ). This pathway is closely associated with neuronal survival as activation results in phosphorylation of proteins associated with apoptosis, such as glycogen synthase kinase‐3β (GSK‐3β) and the Bcl‐2 family (Chen et al, ; Sun et al, ).…”

“…Specifically, we must expand these studies to include females to understand if both males and females respond to both injury and P4 similarly, and if not in what ways do they differ. Developing new therapies for TBI requires understanding the naturally occurring neuroprotective mechanisms (Hellmich et al, ; Kitagishi and Matsuda, ) in more than one or two model species and both sexes. By expanding the types of organisms studied in pre‐clinical TBI studies, we can make greater strides to improving the translational significance of animal models (Schumacher et al, ) with the goals of increasing the success of clinical trials.…”

“…Additionally, P4 mediation is hypothesized to be through the phosphatidylinositol 3‐kinase (PI3K)‐protein kinase B (Akt) signaling pathway, which promotes cell survival and inhibits p53‐mediated apoptosis (Figure ; Du and Montminy, ; Song et al, ). Following activation of the PI3K pathway, the major second messenger (phosphatidylinositol 3,4,5,‐triphosphate [PIP3]) increases expression at the membrane and causes AKT to co‐localize, resulting in its kinase‐mediated phosphorylation and activation (Howes et al, ; Kitagishi and Matsuda, ; Matsuda et al, ). The activated AKT phosphorylates target proteins involved in cell survival, cell cycling, angiogenesis, and metabolism for neuroprotection (Kitagishi and Matsuda, ; Li et al, ).…”

“…Following activation of the PI3K pathway, the major second messenger (phosphatidylinositol 3,4,5,‐triphosphate [PIP3]) increases expression at the membrane and causes AKT to co‐localize, resulting in its kinase‐mediated phosphorylation and activation (Howes et al, ; Kitagishi and Matsuda, ; Matsuda et al, ). The activated AKT phosphorylates target proteins involved in cell survival, cell cycling, angiogenesis, and metabolism for neuroprotection (Kitagishi and Matsuda, ; Li et al, ). These pathways also appear to interact, activating p38α‐MAPK14 and PI3K/Akt signaling pathways to converge in the modulation of NFκB transcriptional activity and increase transcription of COX‐2 (Mercau et al, ; Xu et al, ).…”

Traumatic Brain Injury-Induced Neuronal Apoptosis is Reduced Through Modulation of PI3K and Autophagy Pathways in Mouse by FTY720

“…It has been well documented that the PI3K/AKT pathway was involved in TBI-induced apoptosis (Kitagishi and Matsuda 2013), and neuroprotective drugs activating the PI3K/AKT axis putatively suppress apoptosis (Ishrat et al 2012). Therefore, we investigated the effects of FTY720 on the activation of this pathway.…”