A carregar...
Projeto de investigação
Sem título
Financiador
Autores
Publicações
Beyond sialylation
Publication . Pereira, Beatriz L.; Barbosa, Mariana; Granjo, Pedro; Lochmüller, Hanns; Videira, Paula A.; DCV - Departamento de Ciências da Vida; UCIBIO - Applied Molecular Biosciences Unit; Elsevier Science B.V., Amsterdam.
Defects in sialic acid metabolism disrupt the sialylation of glycoproteins and glycolipids, contributing to a spectrum of diseases, including GNE myopathy (GNEM). This rare disorder is caused by mutations in the GNE gene that encodes for a bifunctional enzyme required for sialic acid biosynthesis, resulting in progressive muscle atrophy and weakness. There is no approved treatment for GNEM, and the number of affected individuals is underestimated. Although hyposialylation is considered the hallmark of GNEM, evidence showed lack of consistent correlation with GNEM severity and unveiled additional roles of GNE that contribute to the onset and/or progression of GNEM. Recent findings indicate that these mechanisms extend beyond glycosylation, encompassing cytoskeletal dynamics, oxidative stress, and muscle regeneration pathways. Understanding how GNE mutations result in a cascade of cellular and molecular dysregulations is crucial for developing targeted therapies aimed at improving the quality of life of patients. This review comprehensively examines GNEM's pathophysiology, clinical presentation, and therapeutic strategies, highlighting key findings on non-canonical GNE functions that account to GNEM clinical outcomes and emerging therapeutic targets. We propose future research directions to explore alternative target pathways that can ultimately support clinical development.
The role of sialoglycans in modulating dendritic cell function and tumour immunity
Publication . Silva, Zélia; Soares, Cátia O.; Barbosa, Mariana; Palma, Angelina S.; Marcelo, Filipa; Videira, Paula A.; UCIBIO - Applied Molecular Biosciences Unit; DCV - Departamento de Ciências da Vida; DQ - Departamento de Química; Academic Press
Dendritic cells (DCs) are crucial for initiating immune responses against tumours by presenting antigens to T cells. Glycosylation, particularly sialylation, plays a significant role in regulating cell functions, by modulating protein folding and signalling. This review aimed to provide a comprehensive overview of how sialic acids influence key aspects of DC biology, including maturation, migration, antigen presentation, and T cell interactions. Sialic acids influence DC endocytosis, affecting their ability to uptake and present antigens, while guiding their migration to lymph nodes and inflamed tissues. Removing sialic acids enhances DC-mediated antigen presentation to T cells, potentially boosting immune responses. Additionally, sialylated glycans on DCs modulate immune checkpoints, which can impact tumour immunity. Hypersialylation of tumour mucins further promotes immune evasion by interacting with DCs. Understanding the interplay between sialylation and DC functions offers promising avenues for enhancing cancer immunotherapy.
Advancing Non-Invasive Colorectal Cancer Screening
Publication . Caldevilla, Renato; Eiras, Mariana; Santos, Daniela A. R.; Almeida, João; Oliveira, Beatriz; Loureiro, Susana; Soares, Janine; Gonzalez-Santos, Miguel; Ramos, Nuno; Videira, Paula A.; Santos, Lúcio Lara; Dinis-Ribeiro, Mário; Lima, Luís; DCV - Departamento de Ciências da Vida; UCIBIO - Applied Molecular Biosciences Unit; MDPI - Multidisciplinary Digital Publishing Institute
Early detection of colorectal cancer (CRC) significantly improves overall prognosis and increases 5-year survival rates up to 90%. Current non-invasive screening methods for CRC, such as the Faecal Immunohistochemical Test (FIT), have some drawbacks, namely, low sensitivity and a high false-positive rate. The Sialyl-Tn (STn) antigen, frequently expressed in pre-malignant lesions and adenocarcinomas, has been shown to be detected by the novel monoclonal antibody L2A5. In this study, we explored the potential of L2A5 as a non-invasive CRC screening method in an attempt to overcome current limitations. The subjects were categorised into four groups based on colonoscopy findings: no lesion (NL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and colorectal cancer (CRC). Slot blot analysis using the L2A5 antibody was performed on stool samples from 95 colonoscopy patients. Our findings showed a differential STn expression between the different clinical groups, evidencing excellent discrimination between NL and CRC (AUC, 0.8252; 95% CI: 0.6983-0.9521; sensitivity, 70%). Moreover, moderate discrimination between the NL+LGD and HGD+CRC groups was discerned (AUC, 0.7766; 95% CI: 0.6792-0.8740; sensitivity, 58%). These findings support the application of L2A5 as a tool for detecting STn, allowing for the identification of advanced lesions in non-invasive CRC screening.
Unidades organizacionais
Descrição
Palavras-chave
Contribuidores
Financiadores
Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
3599-PPCDT
Número da atribuição
2022.04607.PTDC