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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


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.