Browsing by Author "Santos, Nuno C."
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- Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathiesPublication . Vicente Miranda, Hugo; Szego, Éva M.; Oliveira, Luís M.A.; Breda, Carlo; Darendelioglu, Ekrem; de Oliveira, Rita M.; 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; Lashuel, Hilal A.; 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.
- Wolbachia Screening in Aedes aegypti and Culex pipiens Mosquitoes from Madeira Island, PortugalPublication . Fernandes, Rita; Melo, Tiago; Marques Zé-Zé, Líbia Maria; Campos Freitas, Inês; Silva, Manuel; Dias, Eva; Santos, Nuno C.; Gouveia, Bruna R.; Seixas, Gonçalo; Costa Osório, HugoSimple Summary: Mosquitoes can spread serious diseases like dengue and West Nile virus. On Madeira Island, two mosquito species—Aedes aegypti and Culex pipiens—are present and may pose a risk to public health. Scientists are exploring new ways to control these mosquitoes using a natural bacterium called Wolbachia, which can reduce a mosquito’s ability to transmit viruses and even lower mosquito populations. However, for these methods to work, it is important to know first if the mosquitoes in the area already carry this bacterium. In this study, we tested Ae. aegypti and Cx. pipiens from Madeira for Wolbachia. Wolbachia was absent in all 100 Ae. aegypti tested but present in all 40 Cx. pipiens. We also found that the Wolbachia in Cx. pipiens belonged to a group commonly seen in other parts of the world. These results are important because they help us understand which mosquito control strategies might work in Madeira. Specifically, if scientists want to use Wolbachia to control Ae. aegypti on the island, they would need to introduce it artificially. This information can help improve public health efforts and reduce the risk of mosquito-borne diseases in the region.