Analysis of mitophagy in a cellular model of protein aggregation associated with neurodegeneration

• Grant number: 17/14273-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2017
• Effective date (End): July 31, 2018
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Merari de Fátima Ramires Ferrari
• Grantee: Karla Pacheco de Melo
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

It is known that there is accumulation of proteins in the intra- and extracellular environment during aging, and it is believed that the impairment of protein quality contributes to the cellular events that culminate in neurodegeneration. The presence of these protein aggregates leads to intracellular damage including mitochondrial dysfunction, deficiency in its traffic, biogenesis and degradation, contributing to cytotoxicity, increased oxidative stress, energy deprivation and neurodegeneration. Pink1 and Parkin are proteins associated with the labeling and targeting of mitochondria for degradation. In this sense, the purpose of the present study is to evaluate the mitophagy in vitro (primary cell culture of substantia nigra, hipoccampus and locus coeruleus), by the analysis of Pink1 and Parkin with co-localization with lysosomes. The cells will be exposed to rotenone, which favors protein aggregation, characteristic of aging and most neurodegenerative diseases. The aim of the present project is to advance knowledge about the cellular events associated with neurodegeneration with a focus on targeting and degradation of mitochondria in the early stages of protein aggregation. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MELO, KARLA P.; SILVA, CAROLLINY M.; ALMEIDA, MICHAEL F.; CHAVES, RODRIGO S.; MARCOURAKIS, TANIA; CARDOSO, SANDRA M.; DEMASI, MARILENE; NETTO, LUIS E. S.; FERRARI, MERARI F. R.. Mild Exercise Differently Affects Proteostasis and Oxidative Stress on Motor Areas During Neurodegeneration: A Comparative Study of Three Treadmill Running Protocols. NEUROTOXICITY RESEARCH, v. 35, n. 2, p. 410-420, FEB 2019. (13/08028-1, 15/18961-2, 11/06434-7, 11/15281-0, 11/15283-2, 17/14273-0, 11/00478-2)

LIMA, NATHAN C. R.; MELO, THAIANY Q.; SAKUGAWA, ANDRESSA Y. S.; MELO, KARLA P.; FERRARI, MERARI F. R.. Restoration of Rab1 Levels Prevents Endoplasmic Reticulum Stress in Hippocampal Cells during Protein Aggregation Triggered by Rotenone. Neuroscience, v. 419, p. 5-13, NOV 1 2019. (17/14273-0, 13/08028-1, 15/10892-1, 11/06434-7, 15/18961-2)