PHOSPHOINOSITIDE 3-KINASE SIGNALING IN NEURONAL INJURY

SALVADOR, G

Puerto Iguazu

Congreso; 56th International Conference in the Bioscience of Lipids.; 2015

ICBL stirring commitee

PHOSPHOINOSITIDE 3-KINASE SIGNALING IN NEURONAL INJURY Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB-UNS-CONICET), B. Blanca, Argentina.Phosphoinositide-3-kinase (PI3K) catalyzes phosphatidylinositol (PI) phosphorylation in order to produce 3-phosphorylated lipid messengers. The increased level of PI(3,4,5)P3 initiates a number of signaling pathways by recruiting other kinases, such as Akt, to the plasma membrane. In the nervous system, PI3K pathway regulates key neuronal functions such as synaptic plasticity and survival. In the last years, we have been studying the outcome of PI3K pathway in injury conditions that mimic Alzheimer?s disease (AD) neuronal status. Tyrosine phosphorylation associated with PI3K activation is stimulated in synaptic endings exposed to oxidative stress (OS). Increased synaptic PI(3,4,5)P3 levels activate key effectors such as Akt, ERK1/2 and GSK3β. PI3K activity and nuclear localization are also increased in hippocampal neurons exposed to OS. Activated PI3K triggers Akt nuclear translocation and phosphorylation and inactivation of Foxo3A transcription factor, which prevents neuronal death. Neuronal survival mechanisms also comprises the regulation of antioxidant defenses by PI3K through the maintenance of glutathione levels. Nanomolar concentration of oligomeric amyloid β peptide also triggers the phosphorylation of insulin receptor, which results in the subsequent PI3K/Akt activation and Foxo3A nuclear exclusion. Our results show that in conditions that simulate AD neuronal damage, PI3K governs the regulation of multiple effectors thus orchestrating cellular fate.