Constructions of a plasmid with RAGE receptor for the insertion into mammalian cells

• Grant number: 17/17204-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): December 01, 2017
• Effective date (End): November 30, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Giselle Cerchiaro
• Grantee: Gabriela Trindade Coutinho
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Glycation is the binding of free amino groups of proteins with a reducing sugar, such as glucose, and results in the formation of the Advanced Glycation End-produts (AGEs). Recent studies show that AGEs play a role in Alzheimer's disease (AD), since amyloid precursor protein (APP) is also regulated by these advanced glycation end products in vitro and in vivo. The cells have a mechanism to remove and degrade AGEs, by the interaction of these species with receptors. The receptor that acts directly in the AGEs and is the most characterized in the literature is the RAGE. However, RAGE does not destroy AGEs, but it does induce a signal of proinflammation, which depending on the cell type, results in several responses, among them increased expression of RAGE. As an example, this receptor binds fibrillar material (Amyloid peptide, among others) and this amyloid deposit results in an increase in RAGE expression. In patients with Alzheimer's disease, RAGE expression levels are increased in neurons and gliomas. Thus, this IC project aims to construct a plasmid containing the RAGE protein gene for subsequent expression in mammalian cells using the lentiviral system, aiming to create cell lines with the ability to overexpress the RAGE, and thus contribute in a way to understanding of the mechanism of action of this receptor. (AU)