20 documents found, page 1 of 2
A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic ...
Fonseca-Gomes, João; Costa-Coelho, Tiago; Ferreira-Manso, Mafalda; Inteiro-Oliveira, Sara; Vaz, Sandra H.; Alemãn-Serrano, NunoIn Alzheimer's disease (AD), amyloid β (Aβ)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology seve...
Dengue virus capsid protein facilitates genome compaction and packaging
Boon, Priscilla L. S.; Silva Martins, Ana; Lim, Xin Ni; Enguita, Francisco J.; Santos, Nuno C.; Bond, Peter J.; Wan, Yue; Martins, Ivo C.Dengue virus (DENV) is a single-stranded (+)-sense RNA virus that infects humans and mosquitoes, posing a significant health risk in tropical and subtropical regions. Mature virions are composed of an icosahedral shell of envelope (E) and membrane (M) proteins circumscribing a lipid bilayer, which in turn contains a complex of the approximately 11 kb genomic RNA with capsid (C) proteins. Whereas the structure o...
Lipid membrane-based therapeutics and diagnostics
Carvalho, Patricia; Makowski, Marcin; Domingues, Marco; Martins, Ivo C.; Santos, Nuno C.Success rates in drug discovery are extremely low, and the imbalance between new drugs entering clinical research and their approval is steadily widening. Among the causes of the failure of new therapeutic agents are the lack of safety and insufficient efficacy. On the other hand, timely disease diagnosis may enable an early management of the disease, generally leading to better and less costly outcomes. Severa...
Islet amyloid polypeptide & amyloid beta peptide roles in Alzheimer’s disease :...
Martins, Ivo C.; Menezes, Regina; Ferreira, Sofia; Raimundo, Ana F.Alzheimer’s disease (AD) is a neurodegenerative disorder that affects millions worldwide. Due to population ageing, the incidence of AD is increasing. AD patients develop cognitive decline and dementia, features for which is known, requiring permanent care. This poses a major socio-economic burden on healthcare systems as AD patients’ relatives and healthcare workers are forced to cope with rising numbers of af...
The pseudo-circular genomes of Flaviviruses: structures, mechanisms, and functi...
De Falco, Louis; Silva, Nelly; Santos, Nuno C.; Huber, Roland G.; Martins, Ivo C.The circularization of viral genomes fulfills various functions, from evading host defense mechanisms to promoting specific replication and translation patterns supporting viral proliferation. Here, we describe the genomic structures and associated host factors important for flaviviruses genome circularization and summarize their functional roles. Flaviviruses are relatively small, single-stranded, positive-sen...
Dengue and Zika viruses : epidemiological history, potential therapies, and pro...
Silva, Nelly; Santos, Nuno C.; Martins, Ivo C.Dengue virus (DENV), which can lead to fatal hemorrhagic fever, affects 390 million people worldwide. The closely related Zika virus (ZIKV) causes microcephaly in newborns and Guillain-Barré syndrome in adults. Both viruses are mostly transmitted by Aedes albopictus and Aedes aegypti mosquitoes, which, due to globalization of trade and travel alongside climate change, are spreading worldwide, paving the way to ...
West Nile virus capsid protein interacts with biologically relevant host lipid ...
Martins, Ana S.; Carvalho, Filomena Almeida; Faustino, André F.; Martins, Ivo C.; Santos, Nuno C.West Nile and dengue viruses are closely related flaviviruses, originating mosquito-borne viral infections for which there are no effective and specific treatments. Their capsid proteins sequence and structure are particularly similar, forming highly superimposable α-helical homodimers. Measuring protein-ligand interactions at the single-molecule level yields detailed information of biological and biomedical re...
Fast NMR method to probe solvent accessibility and disordered regions in proteins
Faustino, André F.; Barbosa, Glauce M.; Silva, Micael; Castanho, Miguel; Da Poian, Andrea T .; Cabrita, Eurico J.; Santos, Nuno C.; Almeida, Fabio C. L.Understanding protein structure and dynamics, which govern key cellular processes, is crucial for basic and applied research. Intrinsically disordered protein (IDP) regions display multifunctionality via alternative transient conformations, being key players in disease mechanisms. IDP regions are abundant, namely in small viruses, allowing a large number of functions out of a small proteome. The relation betwee...
Structural and functional properties of the capsid protein of Dengue and relate...
Faustino, André F.; Silva Martins, Ana; Karguth, Nina; Artilheiro, Vanessa; Enguita, Francisco J.; Ricardo, Joana; Santos, Nuno C.; Martins, Ivo C.Dengue, West Nile and Zika, closely related viruses of the Flaviviridae family, are an increasing global threat, due to the expansion of their mosquito vectors. They present a very similar viral particle with an outer lipid bilayer containing two viral proteins and, within it, the nucleocapsid core. This core is composed by the viral RNA complexed with multiple copies of the capsid protein, a crucial structural...
Methods for lipid droplet biophysical characterization in Flaviviridae infections
Martins, Ana S.; Martins, Ivo C.; Santos, Nuno C.Lipid droplets (LDs) are intracellular organelles for neutral lipid storage, originated from the endoplasmic reticulum. They play an essential role in lipid metabolism and cellular homeostasis. In fact, LDs are complex organelles, involved in many more cellular processes than those initially proposed. They have been extensively studied in the context of LD-associated pathologies. In particular, LDs have emerged...