Evaluation of molecules from marine animals in the modulation of autophagy-lysosomal system of neurons, with focus on neurodegenerative diseases

• Grant number: 24/10076-9
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Juliana Mozer Sciani
• Grantee: Juliana Mozer Sciani
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
• Associated researchers: Fernanda Caldas Cardoso ; Giovanna Barbarini Longato ; José Roberto Machado Cunha da Silva

Abstract

Alzheimer's disease (AD) and Parkinson's disease (PD) have in common the accumulation of aggregated and misfolded amyloid plaque proteins and ¿-synuclein, respectively, which cause dysfunction of several organelles, including lysosomes, and consequently neuronal death. In a previous project, we obtained extracts and molecules that disaggregate amyloid peptide and lysosomal enzyme modulators from marine animals, which were able to inhibit amyloid peptide-induced neuronal death. In this project, the molecules will be evaluated for modulation of the autophagy-lysosomal pathway for the removal of protein aggregates and neuroprotection. Differentiated SH-SY5Y neurons exposed to oligomerized A¿-42 peptide or rotenone, which induces abundant ¿-synuclein synthesis, will be used. Molecules from marine animals will be incubated and neurons will be evaluated for their viability and type of death. Lysosome integrity and activity will be assessed by fluorescence microscopy and flow cytometry for morphological and functional analysis, in addition to verifying the formation of autophagy vesicles. Proteins of the autophagy pathway will also be assessed by Western blotting. The activity of cathepsins B and L of neurons will be determined before and after treatment with new molecules, which will also be assessed for their ability to interact with ion channels important for lysosomal activity. Thus, it is expected to obtain molecules that can modulate the autophagy-lysosomal system of neurons exposed to protein aggregates of AD and PD, in order to find new targets and treatment possibilities for these incurable diseases. (AU)