Browsing by Author "Santos, Nuno C."
Now showing 1 - 4 of 4
Results Per Page
Sort Options
- Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathiesPublication . Miranda, Hugo Vicente; Szegő, Éva M.; Oliveira, Luís M. A.; Breda, Carlo; Darendelioglu, Ekrem; Oliveira, Rita M. de; Ferreira, Diana G.; Gomes, Marcos A.; Rott, Ruth; Oliveira, Márcia; Munari, Francesca; Enguita, Francisco J.; Simões, Tânia; Rodrigues, Eva F.; Heinrich, Michael; Martins, Ivo C.; Zamolo, Irina; Riess, Olaf; Cordeiro, Carlos; Ponces-Freire, Ana; Santos, Nuno C.; Lopes, Luisa V.; Xiang, Wei; Jovin, Thomas M.; Penque, Deborah; Engelender, Simone; Zweckstetter, Markus; Klucken, Jochen; Giorgini, Flaviano; Quintas, Alexandre; Outeiro, Tiago F.α-Synuclein misfolding and aggregation is a hallmark in Parkinson’s disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced α-synuclein toxicity in vitro and in vivo, in Drosophila and in mice. Glycation affected primarily the N-terminal region of α-synuclein, reducing membrane binding, impaired the clearance of α-synuclein, and promoted the accumulation of toxic oligomers that impaired neuronal synaptic transmission. Strikingly, using glycation inhibitors, we demonstrated that normal clearance of α-synuclein was re-established, aggregation was reduced, and motor phenotypes in Drosophila were alleviated. Altogether, our study demonstrates glycation constitutes a novel drug target that can be explored in synucleinopathies as well as in other neurodegenerative conditions.
- Molecular biomarkers associated with respiratory insufficiency in amyotrophic lateral sclerosisPublication . Pronto-Laborinho, Ana Catarina; Lopes, Catarina S.; Santos, Nuno C.; Carvalho, Filomena A.; Carvalho, Mamede de
- Neuroprotective effects on microglia and insights into the structure–activity relationship of an antioxidant peptide isolated from Pelophylax pereziPublication . Plácido, Alexandra; Amaral, Constança do Pais do; Teixeira, Cátia; Nogueira, Ariane; Brango-Vanegas, José; Barbosa, Eder Alves; Moreira, Daniel C.; Silva-Carvalho, Amanda É.; Silva, Maria da Gloria da; Dias, Jhones do Nascimento; Albuquerque, Patrícia; Saldanha-Araújo, Felipe; Lima, Filipe C. D. A.; Batagin-Neto, Augusto; Kuckelhaus, Selma; Bessa, Lucinda J.; Freitas, Jaime; Brand, Guilherme Dotto; Santos, Nuno C.; Relvas, João B.; Gomes, Paula; Leite, José Roberto S. A.; Eaton, PeterTryptophyllins constitute a heterogeneous group of peptides that are one of the first classes of peptides identified from amphibian’s skin secretions. Here, we report the structural characterization and antioxidant properties of a novel tryptophyllin-like peptide, named PpT-2, isolated from the Iberian green frog Pelophylax perezi. The skin secretion of P. perezi was obtained by electrical stimulation and fractionated using RP-HPLC. De novo peptide sequencing was conducted using MALDI MS/MS. The primary structure of PpT-2 (FPWLLS-NH2) was confirmed by Edman degradation and subsequently investigated using in silico tools. PpT-2 shared physicochemical properties with other well-known antioxidants. To test PpT-2 for antioxidant activity in vitro, the peptide was synthesized by solid phase and assessed in the chemical-based ABTS and DPPH scavenging assays. Then, a flow cytometry experiment was conducted to assess PpT-2 antioxidant activity in oxidatively challenged murine microglial cells. As predicted by the in silico analyses, PpT-2 scavenged free radicals in vitro and suppressed the generation of reactive species in PMA-stimulated BV-2 microglia cells. We further explored possible bioactivities of PpT-2 against prostate cancer cells and bacteria, against which the peptide exerted a moderate antiproliferative effect and negligible antimicrobial activity. The biocompatibility of PpT-2 was evaluated in cytotoxicity assays and in vivo toxicity with Galleria mellonella. No toxicity was detected in cells treated with up to 512 µg/ml and in G. mellonella treated with up to 40 mg/kg PpT-2. This novel peptide, PpT-2, stands as a promising peptide with potential therapeutic and biotechnological applications, mainly for the treatment/prevention of neurodegenerative disorders.
- Role of fibrinogen–erythrocyte and erythrocyte–erythrocyte adhesion on cardiovascular pathologiesPublication . Carvalho, Filomena A.; Guedes, Ana Filipa; Sargento, Luís; Nogueira, J. Braz; Lousada, Nuno; Moreira, Carlos; Santos, Nuno C.