Evaluation of NMNAT2 expression: on hippocampus neurons: targeting on future therapeutical approaches

• Grant number: 18/01251-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Effective date (Start): March 30, 2018
• Effective date (End): July 29, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Elaine Aparecida Del Bel Belluz Guimarães
• Grantee: Gabriel Henrique Dias de Abreu
• Supervisor: Hui-Chen Lu
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Indiana University, United States
• Associated to the scholarship: 17/05361-2 - Role of Toll-like receptor 4 (TLR4) in neuroinflammation and L-DOPA induced dyskinesia in mice, BP.IC

Abstract

In the recent few years, several molecules have been described as key factors in the optimal brain function to work as a robust mechanism against various stress conditions and insults. The nicotinamide mononucleotide adenylyl transferase family (NMNATs) can act as enzymes via NAD+ synthase, as chaperones and even as neuroprotective molecules when overexpressed in mammalian brains. Recent studies revealed that nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) plays an important role in neuroprotection against neurodegenerative disease such as Alzheimer's disease and Parkinson's disease. Moreover, studies have pointed out reduced levels of NMNAT2 in Alzheimer's disease brains, being able to lead to a dementia state. Furthermore, a recent work has described 24 positive and 13 negative NMNAT2 modulators that may be used as tools to better understand the NMNAT2 pathway and further propose a better approach for targeting NMNAT2 in various animal models for neurological disorders. We focus on better understand the expression of NMNAT2 on hippocampus of genetic modified mice through RNA purification, cDNA synthesis, real-time PCR and validate a few genes using RNA sequencing that may be involved in NMNAT2 disrupted pathway. Lastly, to follow up the analysis, immunoblotting and confocal microscopic analysis will be performed to evaluate the distribution and changes and facilitated future analysis. (AU)