About the research:
The project investigates how the control of brain protein synthesis contributes to cognitive resilience in Alzheimer’s disease. Evidence shows that some elderly individuals display amyloid plaques and tau tangles without developing dementia, suggesting the existence of compensatory mechanisms in the brain. The research proposes to identify mRNA translation signatures associated with resilience, using ribosome profiling in human cortical samples. In addition, the study examines how soluble forms of β-amyloid and tau modulate these translational profiles in brain tissue. By shifting the focus from classical pathology to cellular adaptation mechanisms, the project seeks to reveal new biological principles of resilience to dementia, with the potential to guide innovative therapeutic strategies.
Awards and honors:
🏆 CAPES Vital Brazil Grand Thesis Prize, Biological Sciences, CAPES (2017)
🏆 Affiliated Member, Brazilian Academy of Sciences (2021)
🏆 Blas Frangione Early Career Achievement Award, Alzheimer’s Association (2022)
🏆 11 Early Career Researchers to Watch, Nature Medicine (2022)
🏆 1st Featured Researcher Award – Brazil Conference at Harvard University & MIT (2023)
Selected publications:
Bigio B, Lima-Filho RAS, Barnhill O, Sudo FK, Drummond C, Assunção N, Vanderborght B, Beasley J, Young S, Korman A, Jones DR, Sultzer DL, Ferreira ST, Mattos P, Head E, Tovar-Moll F, De Felice FG, Lourenco MV, Nasca C. Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer’s disease in two independent study cohorts. Mol Psychiatry. 2025 Jun;30(6):2573-2583. doi: 10.1038/s41380-024-02862-5. Epub 2025 Jan 7. PMID: 39774493.
Isaac AR, Chauvet MG, Lima-Filho R, Wagner BA, Caroli BG, Leite REP, Suemoto CK, Nunes PV, De Felice FG, Ferreira ST, Lourenco MV. Defective regulation of the eIF2-eIF2B translational axis underlies depressive-like behavior in mice and correlates with major depressive disorder in humans. Transl Psychiatry. 2024 Oct 1;14(1):397. doi: 10.1038/s41398-024-03128-y. PMID: 39349438; PMCID: PMC11442801.
Lourenco MV, Frozza RL, de Freitas GB, Zhang H, Kincheski GC, Ribeiro FC, Gonçalves RA, Clarke JR, Beckman D, Staniszewski A, Berman H, Guerra LA, Forny-Germano L, Meier S, Wilcock DM, de Souza JM, Alves-Leon S, Prado VF, Prado MAM, Abisambra JF, Tovar-Moll F, Mattos P, Arancio O, Ferreira ST, De Felice FG. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models. Nat Med. 2019 Jan;25(1):165-175. doi: 10.1038/s41591-018-0275-4. Epub 2019 Jan 7. PMID: 30617325; PMCID: PMC6327967.
Oliveira MM, Lourenco MV, Longo F, Kasica NP, Yang W, Ureta G, Ferreira DDP, Mendonça PHJ, Bernales S, Ma T, De Felice FG, Klann E, Ferreira ST. Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer’s disease. Sci Signal. 2021 Feb 2;14(668):eabc5429. doi: 10.1126/scisignal.abc5429. PMID: 33531382; PMCID: PMC8317334.
Lourenco MV, Clarke JR, Frozza RL, Bomfim TR, Forny-Germano L, Batista AF, Sathler LB, Brito-Moreira J, Amaral OB, Silva CA, Freitas-Correa L, Espírito-Santo S, Campello-Costa P, Houzel JC, Klein WL, Holscher C, Carvalheira JB, Silva AM, Velloso LA, Munoz DP, Ferreira ST, De Felice FG. TNF-α mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s β-amyloid oligomers in mice and monkeys. Cell Metab. 2013 Dec 3;18(6):831-43. doi: 10.1016/j.cmet.2013.11.002. PMID: 24315369.
