Study of autophagy as the driving mechanism of neurodegenerative diseases

• Grant number: 15/18961-2
• Support type: Regular Research Grants
• Duration: July 01, 2016 - June 30, 2018
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Merari de Fátima Ramires Ferrari
• Grantee: Merari de Fátima Ramires Ferrari
• Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

It is believed that the loss of the protein quality control impairs the cellular events culminating in neurodegeneration. In view of this, the purpose of the present study is to evaluate the cellular quality control system in in vitro (primary cell culture) and in vivo (before the onset of neurodegeneration symptoms) models of sporadic (using rotenone) and familial neurodegenerative diseases such as Amyotrophic Lateral Sclerosis associated with SOD1 gene mutations, and Alzheimer's disease related to triplicated copies of important genes for this neurodegenerative disease using a mice model of Down syndrome. To this end, levels of proteins associated with activation of autophagy will be analyzed (including mitophagy), autophagy vesicles trafficking and autophagy flux will be also quantified. Additionally, it is intended to examine the role of BAG-2 protein (a co-chaperone that binds to the hsp70 to protein degradation) to modulate the autophagic activity before protein aggregation, as well as the role of physical activity on autophagy in the course of sporadic neurodegeneration as a therapeutic / preventive strategy. (AU)

Scientific publications

(5)

(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)

CHAVES, JULIANA C. S.; MACHADO, FELIPPE T.; ALMEIDA, MICHAEL F.; BACOVSKY, TATIANA B.; FERRARI, MERARI F. R. microRNAs expression correlates with levels of APP, DYRK1A, hyperphosphorylated Tau and BDNF in the hippocampus of a mouse model for Down syndrome during ageing. Neuroscience Letters, v. 714, JAN 1 2020. Web of Science Citations: 0.

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. Web of Science Citations: 0.

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. Web of Science Citations: 1.

MELO, THAIANY QUEVEDO; COPRAY, SJEF J. C. V. M.; FERRARI, MERARI F. R. Alpha-Synuclein Toxicity on Protein Quality Control, Mitochondria and Endoplasmic Reticulum. Neurochemical Research, v. 43, n. 12, p. 2212-2223, DEC 2018. Web of Science Citations: 5.

ALMEIDA, MICHAEL F.; SILVA, CAROLLINY M.; D'UNHAO, ALINE M.; FERRARI, MERARI F. R. Aged Lewis rats exposed to low and moderate doses of rotenone are a good model for studying the process of protein aggregation and its effects upon central nervous system cell physiology. Arquivos de Neuro-Psiquiatria, v. 74, n. 9, p. 737-744, SEP 2016. Web of Science Citations: 3.