Bioprospecting of potential neuroprotective agents purified from spider and snake venoms in 3xTg-AD mice - a model of Alzheimer's disease.

• Grant number: 25/10558-6
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2027
• Field of knowledge: Biological Sciences - Zoology - Applied Zoology
• Principal Investigator: Wagner Ferreira dos Santos
• Grantee: Wagner Ferreira dos Santos
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Venoms represent a sophisticated biochemical arsenal, the result of millions of years of evolution, and harbor a remarkable diversity of molecules with high bioactive potential. These natural compounds have emerged both as promising candidates for new drugs and as valuable tools for pharmacological research. In this project, we explore the neuroprotective and anti-amyloid potential of acylpolyamines such as Parawixin10 (Pwx10) and Mygalin, isolated from spiders, as well as peptides and proteins derived from snake venoms. The experimental strategy includes in vitro Thioflavin T aggregation assays for A¿ fibril detection, cell viability tests using differentiated SH-SY5Y cell lines, and in vivo experimentation with triple-transgenic Alzheimer's disease mice (3xTg-AD), subjected to behavioral assessments in the Elevated Plus Maze and Novel Object Recognition Test. Additionally, experiments will be conducted to evaluate nervous tissue integrity under the influence of these molecules. This study is pioneering in the prospecting of neuroactive compounds derived from animal toxins for the treatment of neurodegenerative diseases and highlights the urgency of biodiversity conservation as a strategic resource for Translational Biology. With this project, our laboratory takes a qualitative leap in cross-species comparative approaches by incorporating a highly relevant genetic model for the study of neurodegenerative diseases. (AU)