Evaluation of PTEN modulation on glutamatergic signaling in neuroinflammation model

• Grant number: 20/08005-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2020
• End date: October 12, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Elisa Mitiko Kawamoto Iwashe
• Grantee: Gabriela Spina Nagy
• Host 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. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NAGY, GABRIELA SPINA; KAWAMOTO, ELISA MITIKO; BRIDI, JESSIKA CRISTINA. The role of PTEN signaling in synaptic function: Implications in autism spectrum disorder. Neuroscience Letters, v. 759, AUG 10 2021. (20/08005-5, 16/07427-8, 19/12974-6, 19/10044-1)