Developing new tools to study the relationship between PTEN and Klotho expression by molecular biological approaches

• Grant number: 17/25279-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: April 01, 2018
• End date: August 01, 2018
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Elisa Mitiko Kawamoto Iwashe
• Grantee: Natalia Prudente de Mello
• Supervisor: Daniel Charles Berwick
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Open University, England
• Associated to the scholarship: 15/25491-2 - Evaluation of the effects of the Klotho protein on the neuronal morphological alteration characteristics of the lack of PTEN protein, BP.MS

Abstract

PTEN, which is essential for embryonic development, is a protein capable of controlling cell growth and proliferation by acting through the PI3K/AKT pathway. Since it has several roles in the development of the central nervous system (CNS), PTEN deletion has been associated with some neurological disorders. In turn, Klotho is a protein associated with longevity that has received increasing attention since its discovery in 1997. Klotho has been shown to downregulate the PI3K/AKT pathway, and it has promising therapeutic potential to improve cognitive function. Recent data obtained in the main project (FAPESP Nº 2015/25491-2) indicate a reduction in either protein in the absence of the other. These data strengthen the hypothesis of using Klotho as a treatment to revert the neuronal morphological alterations characteristics of PTEN deletion. Thus, using molecular biological approaches such as CRISPr and siRNA to genetically modify the human Ren cell VM neural precursor line, the objective of the proposed study is to develop tools for analyzing the molecular mechanisms underlying this relationship, and also replicate the results seen in mice in a human system. Since there is little in the literature to understand how each protein might affect the other's expression or how Klotho modulates neuronal function, we anticipate that data produced can bring new and important information. (AU)