Association of alpha-synuclein aggregates with mitochondria in intercellular communication structures in Parkinson's disease model

• Grant number: 24/11150-8
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: August 15, 2024
• End date: December 14, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Merari de Fátima Ramires Ferrari
• Grantee: Hilton Pires de Camargo Junior
• Supervisor: Linlin Ma
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Griffith University, Australia
• Associated to the scholarship: 21/09781-1 - Analysis of mitochondria recycling in a cell model of Parkinson's Disease, BP.IC

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder that can be triggered by environmental and genetic factors. Alpha-synuclein (a-syn) is a protein encoded by the SNCA gene, in which point mutations (e.g., A53T; A30P; E46K) or gene duplication are associated with the genetic form of PD. Intercellular transfer of a-syn is known to play a role in the progression of PD, and previous studies have described the association of a-syn aggregates with mitochondria during intercellular transport via tunneling nanotubes(TNTs). In our research in Brazil, we observed that in dopaminergic neurons derived from SH-SY5Y cells overexpressing wild-type (WT) and mutant (A30P or A53T) a-syn, mitochondria are smaller, more fragmented, and less interconnected, potentially facilitating their intercellular transport. Considering that the transfer of a-syn aggregates can occur not only through TNTs but also via endo and exocytosis and mediated by glial cells, our goals are to analyze whether the association of a-syn aggregates with mitochondria also occurs in extracellular vesicles in monocultures of SH-SY5Y cells differentiated into dopaminergic neurons, and in TNTs formed between SH-SY5Y cells and C20 microglial cells in co-culture. By doing so we would be able to identify a new pathway for PD progression and to characterize a novel model for a-syn transmission studies, that will be used in new experiments here in Brazi.