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Effects of ±-Klotho protein in TNF-± signaling trough TNFR1 in glia primary culture

Grant number: 19/05970-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2019
Effective date (End): April 30, 2020
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Cristoforo Scavone
Grantee:Giovanna Araujo de Souza
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:16/07427-8 - Aging and neuroprotection: effects of Klotho protein in energetic metabolism, Na,K-ATPase signaling and adaptative response in central nervous system, AP.TEM

Abstract

The highest prevalence of diseases related to aging like Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis, are a result of the increase in life expectancy. Aging is a complex and multifactorial process in which molecular, cellular and behavior alterations can be observed. Inflammation is a common and important factor between many alterations observed in CNS and its response results in the production of inflammatory cytokines like TNF-±. This cytokine has differential physiological action in CNS based on concentration -dependent binding to TNF receptors (TNFR). TNFR1 activate apoptotic pathways and TNFR2 are related with neuroprotection. The ±-Klotho protein is receiving emphasis in literature for its ability to modulate synaptic plasticity and reduce cognitive impairment in health, aging and diseases associated to senescence. Therefore, as ±-klotho is involved in adaptive response in the organism and based on the importance of TNF-± for synaptic plasticity in the CNS, this project investigates if the ±-Klotho protein modulates the signaling of TNF-± in TNFR1 knockout animals in order to decrease inflammation linked to glutamatergic excitotoxicity. This study intends to make progress in the comprehension of neuroinflammation and allow the development of new treatments.