Name of Fellow


SANDRA ISABEL FREITAS MOTA

Institution


Funder


FCT

Contact information of fellow


Country


Portugal

Title of project/programme


H2O2-MEDIATED SRC SIGNALING PATHWAYS IN GLUTAMATERGIC SYNAPSES IN ALZHEIMER'S DISEASE MODELS

Source of funding information


FCT

Total sum awarded (Euro)


€ 107,640

Start date of award


01/01/14

Total duration of award in years


6.0

The project/programme is most relevant to:


Alzheimer's disease & other dementias

Keywords


Research Abstract


Oxidative stress has been consistently associated to Alzheimer’s disease (AD). Amyloid beta peptide (Abeta) generates reactive oxygen species (ROS), which may result from interaction with mitochondria; Abeta also activates N-methyl-D-aspartate receptors (NMDARs), leading to intracellular Ca2+ dyshomeostasis. Importantly, NMDARs are positively regulated by Src Tyr-kinase-mediated phosphorylation. At the presynaptic terminal, Src may regulate neurotransmitter release. In mitochondria, Src phosphorylates respiratory chain components regulating cell survival. Importantly, Src activation is positively modulated by H2O2. Thus, in this project we will evaluate whether Abeta-induced H2O2 production regulates glutamate release and NMDARs through Src activation. We will also determine whether NMDAR activation triggers Src activation through Ca2+-induced H2O2 formation and the role of mitochondrial ROS in Src signaling, using hippocampal cultures and synaptosomes from 3xTg-AD and wild type (WT) mice, and GluN2B(-/-) hippocampal cultures. H2O2-induced activation of Src is expected to play an important role in the regulation of synaptic signaling in AD.

Export as PDF