Synthesis, characterization and evaluation of intracellular peptides in the central nervous system of zebrafish (Danio rerio) in a model of Parkinson's disease

• Grant number: 23/05219-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2023
• End date: March 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Norival Alves Santos Filho
• Grantee: Louise Oliveira Fiametti
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 23/12077-0 - Analysis of the neuroprotective or toxic activity of peptides in a transgenic line of Danio rerio, BE.EP.MS

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, but despite being highlighted in recent research, its cause remains unknown, there is no cure and the available treatments only aim to control the symptoms. Few studies focus on the role of peptides in PD, which have been shown to play a biological role in other neurodegenerative diseases. A previous study demonstrated that 9 of 125 zebrafish brain peptides were altered in a model of 6-hydroxydopamine, considered the neurotoxin that causes a form of PD most similar to those seen in patients. In this context, this Master's project aims to better understand the role of 3 of these 9 peptides. The choice of peptides was based on their precursor proteins, namely: 1) fatty acid protein 7 brain a, which is related to the expression of antioxidant enzymes and protection against apoptosis signaling; 2) mitochondrial ribosomal protein S36, which modified slows cell cycle progression and proliferation; and 3) MARCKS-related protein 1-B, which controls cell movement through regulation of the actin cytoskeleton, among other functions. Peptides will be chemically synthesized in solid phase and analyzes will be performed using Neuro2A cells and in vivo tests with zebrafish. The animal model used will be the Danio rerio larva, which in addition to being translucent, can receive treatment with 6-hydroxydopamine without the need for intracerebral injection, since it does not have a formed blood-brain barrier.