Evaluation of molecules from marine animals in the modulation of ion channels and the autophagy-lysosomal system of neurons, with a focus on neurodegenerative diseases."

• Grant number: 24/15252-0
• Support Opportunities: Scholarships abroad - Research
• Start date: May 01, 2025
• End date: June 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Juliana Mozer Sciani
• Grantee: Juliana Mozer Sciani
• Host Investigator: Fernanda Caldas Cardoso
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
• Institution abroad: University of Queensland, Brisbane (UQ), Australia

Abstract

The marine environment represents a rich and unknown source of new molecules with biotechnological potential, with known action in ionic channels. Some compounds are already in clinical use, which demonstrates the success of these molecules to become medicines. Neurodegenerative diseases, such as Alzheimer's and Parkinson, lack effective pharmacological treatments, as available drugs only prolong the patient's lifetime. These diseases are characterized by altered proteostasis due to the accumulation of protein aggregates, which causes oxidative stress, inflammation and neuronal death. Among several factors, ionic channels are changed in the course of the disease and contribute to the alteration of proteostase, in particular autophagy-lisosomes pathway. This project proposes the study of molecules from marine animals in the modulation of ion channels and the restoration of the autophagy-lysosomal system, with the study of a possible correlation between the two approaches. Natural, synthetic molecules, and fractions of the secretion of marine invertebrates already studied by the group, which do not cause neurotoxicity and inhibit neuronal death caused by A¿42, will be tested in SH-SY5Y neurons to evaluate the modulation of calcium and sodium channels. The active fraction will be re-fractionated and tested again, to obtain a pure active molecule which, together with those isolated natural and synthetic, will be evaluated for their ability to promote lysosome restoration by fluorescence microscopy and flow cytometry assays. Thus, it is expected to find new molecules that restore the autophagy-lysosomal system and modulate ion channels, which, in the future, can be used in the treatment of neurodegenerative diseases."