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Molecular basis of the toxicity of protein oligomers associated to brain amyloidosis

Abstract

Toxic protein oligomers are believed to be the main culprit for the synaptic loss and cognitive decline in proteinopathies afflicting the central nervous system (CNS), as Alzheimer's, Parkinson, and prionoses. As a result, the interaction between oligomers and neurons is now seen as a preferential target for the development of novel therapeutic strategies against these neuropathologies. On the other hand, detailed structure of these toxic species is still unknown, as the molecular events underlying oligomer-elicited neurotoxicity. Here our main goal is to understand the molecular and cellular mechanism linked to the neurotoxicity of protein oligomers associated to diseases. The experimental approach is centered on the use of novel human single chain antibodies able to distinguish toxic oligomers from their non-toxic assemblies’ counterparts. The work will focus on determining the neuroprotection of anti-oligomer scFv's exhibiting distinct specificities for each oligomeric assembly on both in vitro and in vivo models of CNS. Through this approach we hope to significantly contribute to the development of reagents with therapeutic and diagnostic potential against these devastating and still cureless diseases. (AU)

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Scientific publications (4)
(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)
ALMEIDA, GLAUCIA M.; SOUZA, JULIANO P.; MENDES, NIELE D.; PONTELLI, MARJORIE C.; PINHEIRO, NATHALIA R.; NOGUEIRA, GIOVANNA O.; CARDOSO, RICARDO S.; PAIVA, ISADORA M.; FERRARI, GUSTAVO D.; VERAS, FLAVIO P.; CUNHA, FERNANDO Q.; HORTA-JUNIOR, JOSE A. C.; ALBERICI, LUCIANE C.; CUNHA, THIAGO M.; PODOLSKY-GONDIM, GUILHERME G.; NEDER, LUCIANO; ARRUDA, EURICO; SEBOLLELA, ADRIANO. Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response. FRONTIERS IN NEUROSCIENCE, v. 15, NOV 23 2021. Web of Science Citations: 0.
VASCONCELOS, ISRAEL C.; CAMPOS, RAQUEL M.; SCHWAEMMLE, HANNA K.; MASSON, ANA P.; FERRARI, GUSTAVO D.; ALBERICI, LUCIANE C.; FAC, VITOR M.; GARCIA-CAIRASCO, NORBERTO; SEBOLLELA, ADRIANO. Research Article A freeze-and-thaw-induced fragment of the microtubule-associated protein tau in rat brain extracts: implications for the biochemical assessment of neurotoxicity. BIOSCIENCE REPORTS, v. 41, n. 3 MAR 24 2021. Web of Science Citations: 0.
BITENCOURT, ANDRE L. B.; CAMPOS, RAQUEL M.; CLINE, ERIKA N.; KLEIN, WILLIAM L.; SEBOLLELA, ADRIANO. Antibody Fragments as Tools for Elucidating Structure-Toxicity Relationships and for Diagnostic/Therapeutic Targeting of Neurotoxic Amyloid Oligomers. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 23 DEC 2020. Web of Science Citations: 0.
SEBOLLELA, ADRIANO; CLINE, ERIKA N.; POPOVA, IZOLDA; LUO, KEVIN; SUN, XIAOXIA; AHN, JAY; BARCELOS, MILENA A.; BEZERRA, VANESSA N.; LYRA E SILVA, NATALIA M.; PATEL, JASON; PINHEIRO, NATHALIA R.; QIN, LEI A.; KAMEL, JOSETTE M.; WENG, ANTHEA; DINUNNO, NADIA; BEBENEK, ADRIAN M.; VELASCO, PAULINE T.; VIOLA, KIRSTEN L.; LACOR, PASCALE N.; FERREIRA, SERGIO T.; KLEIN, WILLIAM L. A human scFv antibody that targets and neutralizes high molecular weight pathogenic amyloid-beta oligomers. Journal of Neurochemistry, v. 142, n. 6, p. 934-947, SEP 2017. Web of Science Citations: 8.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.