The Interplay of ABC Transporters in Aß Translocation and Cholesterol Metabolism: Implicating Their Roles in Alzheimer's Disease.
Mol Neurobiol
; 58(4): 1564-1582, 2021 Apr.
Article
em En
| MEDLINE
| ID: mdl-33215389
ABSTRACT
The occurrence of Alzheimer's disease (AD) worldwide has been progressively accelerating at an alarming rate, without any successful therapeutic strategy for the disease mitigation. The complexity of AD pathogenesis needs to be targeted with an alternative approach, as provided by the superfamily of ATP-binding cassette (ABC) transporters, which constitutes an extensive range of proteins, capable of transporting molecular entities across biological membranes. These protein moieties have been implicated in AD, based upon their potential in lipid transportation, resulting in maintenance of cholesterol homeostasis. These transporters have been reported to target the primary hallmark of AD pathogenesis, namely, beta-amyloid hypothesis, which is associated with accumulation of beta-amyloid (Aß) plaques in AD patients. The ABC transporters have been observed to be localized to the capillary endothelial cells of the blood-brain barrier and neural parenchymal cells, where they exhibit different roles, consequently influencing the neuronal expression of Aß peptides. The review highlights different families of ABC transporters, ABCB1 (P-glycoprotein), ABCA (ABCA1, ABCA2, and ABCA7), ABCG2 (BCRP; breast cancer resistance protein), ABCG1 and ABCG4, as well as ABCC1 (MRP; multidrug resistance protein) in the CNS, and their interplay in regulating cholesterol metabolism and Aß peptide load in the brain, simultaneously exerting protective effects against neurotoxic substrates and xenobiotics. The authors aim to establish the significance of this alternative approach as a novel therapeutic target in AD, to provide the researchers an opportunity to evaluate the potential aspects of ABC transporters in AD treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Colesterol
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Peptídeos beta-Amiloides
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Transportadores de Cassetes de Ligação de ATP
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Doença de Alzheimer
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Neurobiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Índia