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https://hdl.handle.net/1822/74409
Título: | Emerging insights on the role of V-ATPase in human diseases: Therapeutic challenges and opportunities |
Autor(es): | Cátia S. Pereira Rodrigues, L. R. Côrte-Real, Manuela |
Palavras-chave: | human disorders infections subunit isoforms therapeutic target V-ATPase |
Data: | 2021 |
Editora: | Wiley-Blackwell |
Revista: | Medicinal Research Reviews |
Citação: | Cátia S. Pereira; Rodrigues, Lígia R.; Côrte-Real, Manuela, Emerging insights on the role of V-ATPase in human diseases: Therapeutic challenges and opportunities. Medicinal Research Reviews, 2021. |
Resumo(s): | The control of the intracellular pH is vital for the survival of all organisms. Membrane transporters, both at the plasma and intracellular membranes, are key players in maintaining a finely tuned pH balance between intra- and extracellular spaces, and therefore in cellular homeostasis. V-ATPase is a housekeeping ATP-driven proton pump highly conserved among prokaryotes and eukaryotes. This proton pump, which exhibits a complex multisubunit structure based on cell type-specific isoforms, is essential for pH regulation and for a multitude of ubiquitous and specialized functions. Thus, it is not surprising that V-ATPase aberrant overexpression, mislocalization, and mutations in V-ATPase subunit-encoding genes have been associated with several human diseases. However, the ubiquitous expression of this transporter and the high toxicity driven by its off-target inhibition, renders V-ATPase-directed therapies very challenging and increases the need for selective strategies. Here we review emerging evidence linking V-ATPase and both inherited and acquired human diseases, explore the therapeutic challenges and opportunities envisaged from recent data, and advance future research avenues. We highlight the importance of V-ATPases with unique subunit isoform molecular signatures and disease-associated isoforms to design selective V-ATPase-directed therapies. We also discuss the rational design of drug development pipelines and cutting-edge methodological approaches toward V-ATPase-centered drug discovery. Diseases like cancer, osteoporosis, and even fungal infections can benefit from V-ATPase-directed therapies. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/74409 |
DOI: | 10.1002/med.21782 |
ISSN: | 0198-6325 |
Versão da editora: | https://onlinelibrary.wiley.com/journal/10981128 |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series CBMA - Artigos/Papers |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_54126_1.pdf Acesso restrito! | 2,86 MB | Adobe PDF | Ver/Abrir |