Modulators from marine animal cathepsins B and D as a tool for understanding Alzheimer's disease

• Grant number: 23/14407-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Juliana Mozer Sciani
• Grantee: Juliana Guanaes Pina
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Alzheimer's disease is a neurodegenerative, irreversible condition with an increasing incidence, linked to the rising life expectancy and genetic factors. Presently, there are only four therapies approved by the Food and Drug Administration (FDA), with the current treatment being symptomatic. The pathophysiology of the disease remains uncertain, although various hypotheses are under study, with the primary ones being the formation of ²-amyloid peptide and tau protein, both implicated in neuronal synapse. According to the ²-amyloid peptide hypothesis, the peptide is formed from the amyloid precursor protein following the action of secretases. The resulting peptide undergoes oligomerization, rendering it neurotoxic. Its accumulation leads to the formation of senile plaques in the hippocampal region, ultimately causing neuron death. Lysosomal peptidases, such as cathepsins B and D, are enzymes that regulate lysosomal activity, function to eliminate unwanted proteins from cells. However, when their activity or expression decreases, as seen in degenerative diseases, lysosomal activity diminishes, resulting in the buildup of proteins such as ²-amyloids. Therefore, given the high prevalence of this disease and the necessity for new treatments, this study aims to investigate the activity of cathepsins B and D in neurons exposed to beta-amyloid peptide, utilizing molecules from marine animals previously studied by the group as tools to gain a better understanding of the role of these enzymes in the disease. Consequently, by the end of the project, a better comprehension of lysosomal enzyme function and how their modulation can aid in Alzheimer's disease treatment is anticipated.