The aggregation of the amyloidogenic protein alfa-synuclein involved in Parkinson's Disease

• Grant number: 24/19936-0
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: January 06, 2025
• End date: February 25, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Debora Foguel
• Grantee: Bruno Ferreira Brischi
• Host Institution: Instituto de Bioquímica Médica. Universidade Federal do Rio de Janeiro (UFRJ). Ministério da Educação (Brasil)

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, with more than 5 million people living with the condition. PD is characterized by the progressive loss of dopaminergic neurons in the midbrain region, in the substantia nigra pars compacta. An important histopathological feature of PD is the presence of intracellular protein aggregates known as Lewy bodies (LB). Aggregation of the synaptic protein alpha-synuclein (aSyn) is believed to be directly involved in the process of neuronal loss in PD, since amyloid fibers formed by this protein are the main components of LB. Currently, there are only palliative treatments for patients with PD, so it is necessary to search for new therapeutic alternatives that target events important for neuronal death, such as aSyn aggregation. Based on this need, LAPA has developed projects that aim to study aSyn aggregation using in vitro or in-cell aggregation models. Several studies have been published by the group in recent years. In this sense, the project to be developed by student Bruno Brischi during his internship at LAPA will aim to evaluate the influence of natural compounds of Amazonian origin on the aggregation of the amyloidogenic protein alpha-synuclein, seeking possible new therapeutic alternatives for PD. This project is part of a collaboration that LAPA has been developing with Dr. Ayla Santanna's group from INP, where we have been studying extracts from Euterpe oleracea (açaí) seeds, rich in procyanidins. Initial data from the group show that these extracts have anti-amyloidogenic action, using wild-type aSyn as a model. Now, we intend to advance these analyses using fractions of the extract with procyanidins with different degrees of polymerization in cellular models and C. elegans. This project seemed interesting to us for Bruno's scholarship and internship period, as it will allow the student to come into contact with some structural and cellular biology techniques in a short period of time. (AU)