Evaluation of neuronal-PTEN effects in glutamatergic signaling during neuroinflammation

• Grant number: 23/04906-6
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Elisa Mitiko Kawamoto Iwashe
• Grantee: Elisa Mitiko Kawamoto Iwashe
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Cristoforo Scavone

Abstract

The phosphatase and tensin homolog on chromosome ten (PTEN) is a tumor suppressor acting or not through its phosphatase activity. Studies have concentrated on investigating PTEN mechanisms associated to tumorigenesis. However, due to the wide-ranging characteristics of this phosphatase, which can modulate the protein kinase B (AKT) pathway and transcription factors such as the nuclear factor kappa B (NF-kB), PTEN is also involved in cell survival responses and probably in inflammatory processes. However, little is known about the neuronal molecular mechanisms involved in the PTEN effects on the glutamatergic signaling during inflammation.This study aims to investigate the role of neuronal PTEN in memory and learning and in the signaling mechanisms associated with the N-Methyl-D-Aspartate receptor and the transcription factor NF-kB in the central nervous system (CNS) in the presence or absence of an inflammatory stimulus, represented by the administration of lipopolysaccharide.Studies have shown a strong correlation between inflammation and neuropsychiatric disorders. A better understanding of these physiological processes may contribute to the development of new approaches and strategies for pharmacological interventions aimed at treating diseases associated with the PTEN deletion or mutation, common in many tumors and in autism spectrum disorders, allowing slow the progression of these diseases or develop new therapeutic interventions. (AU)