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Evaluation of PTEN modulation on glutamatergic signaling in neuroinflammation model

Grant number: 20/08005-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2020
Effective date (End): July 31, 2021
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Elisa Mitiko Kawamoto Iwashe
Grantee:Gabriela Spina Nagy
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Neuroinflammation, oxidative stress and excitotoxicity are processes strongly linked to aging and central nervous system (CNS) pathologies like Parkinson´s and Alzheimer´s diseases. The recognition of exogenous or endogenous molecular patterns (such as lipopolysaccharide) by specific receptors in innate immune cell membranes triggers inflammation in CNS. This recognition activates microglial cells inducing translocation of transcription factor nuclear factor kappa b (NF-ºB) that stimulates, inside the nucleus, the production of pro-inflammatory molecules, including oxygen reactive species, which are linked to oxidative stress. The presence of these mediators can also induce glutamate neurotransmitter release, related with excitotoxicity phenomena. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) seems to be related with these neuropathological conditions, being a possible pharmacological target. Previously studies already have demonstrated that mutations in this protein are linked with CNS disturbances, like autism. PTEN plays important roles linked to its action as phosphatase, besides it can modulate cerebral morphology and synaptic plasticity. This protein negatively regulates AKT pathway which modulates several cellular processes including NF-ºB activation, being able to present an important role in inflammation and oxygen reactive species released due to it. Besides, studies also showed that PTEN can possibly have participation in excitotoxicity process. Although studies have been demonstrated PTEN influence on neuroinflammation, data are still contradictory and few understood.