Dysfunction of ABC transporters at the blood-brain barrier: Role in neurological disorders

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 2020

Autores

Gil Martins, E (Autor) Outra; Barbosa, DJ (Autor) Outra; Silva, V (Autor) Outra; Fernando Remiao (Autor) FFUP; Silva, R (Autor) Outra

Revista

Título: PHARMACOLOGY & THERAPEUTICS

Vol. 213

ISSN: 0163-7258

Editora: Pergamon Press - Elsevier

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 19 Citações

Outras Informações

ID Authenticus: P-00S-2YA

DOI: 10.1016/j.pharmthera.2020.107554

Abstract (EN): ABC (ATP-binding cassette) transporters represent one of the largest and most diverse superfamily of proteins in living species, playing an important role in many biological processes such as cell homeostasis, cell signaling, drug metabolism and nutrient uptake. Moreover, using the energy generated from ATP hydrolysis, they mediate the efflux of endogenous and exogenous substrates from inside the cells, thereby reducing their intracellular accumulation. At present, 48 ABC transporters have been identified in humans, which were classified into 7 different subfamilies (A to G) according to their phylogenetic analysis. Nevertheless, the most studied members with importance in drug therapeutic efficacy and toxicity include P-glycoprotein (P-gp), a member of the ABCB subfamily, the multidrug-associated proteins (MPRs), members of the ABCC subfamily, and breast cancer resistance protein (BCRP), a member of the ABCG subfamily. They exhibit ubiquitous expression throughout the human body, with a special relevance in barrier tissues like the blood-brain barrier (BBB). At this level, they play a physiological function in tissue protection by reducing or limiting the brain accumulation of neurotoxins. Furthermore, dysfunction of ABC transporters, at expression and/or activity level, has been associated with many neurological diseases, including epilepsy, multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis. Additionally, these transporters are strikingly associated with the pharmacoresistance to central nervous system (CNS) acting drugs, because they contribute to the decrease in drug bioavailability. This article reviews the signaling pathways that regulate the expression and activity of P-gp, BCRP andMRPs subfamilies of transporters, with particular attention at the BBB level, and their mis-regulation in neurological disorders.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 100