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

Gil-Martins, Eva; Barbosa, Daniel José; Silva, Vera; Remião, Fernando; Silva, Renata

doi:10.1016/j.pharmthera.2020.107554

Cited by 104 publications

(88 citation statements)

References 335 publications

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“…as well as the organ and cell type in which they are expressed. For example, members of the ABCB and ABCC subfamilies are expressed in physiological barriers such as intestine and blood–brain interfaces to restrict the entry or mediate the exit of harmful endogenous molecules or xenobiotics [ 3 , 4 ]. Overexpression of these ABC transporters has been reported in several cancers and is responsible for the multidrug resistance (MDR) phenotype of cancer cells [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Role of ABCA7 in Human Health and in Alzheimer’s Disease

Dib

Pahnke

Gosselet

2021

IJMS

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Several studies, including genome wide association studies (GWAS), have strongly suggested a central role for the ATP-binding cassette transporter subfamily A member 7 (ABCA7) in Alzheimer’s disease (AD). This ABC transporter is now considered as an important genetic determinant for late onset Alzheimer disease (LOAD) by regulating several molecular processes such as cholesterol metabolism and amyloid processing and clearance. In this review we shed light on these new functions and their cross-talk, explaining its implication in brain functioning, and therefore in AD onset and development.

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Section: Introductionmentioning

confidence: 99%

Role of ABCA7 in Human Health and in Alzheimer’s Disease

Dib

Pahnke

Gosselet

2021

IJMS

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“…BBB properties are primarily determined by tight and adherens junctions between the capillary endothelial cells (Stamatovic et al, 2008), and is regulated by the unique surrounding microenvironment (basement membrane, astrocytes, and pericytes) which controls the secretion of a variety of soluble factors that affect transport, signaling, angiogenesis and drug degradation, forming an enzymatic barrier (Eyal et al, 2009;Mehta et al, 2010;Wilhelm et al, 2013). The BBB is known to exclude nearly all molecules from entering the brain except those that are either small or lipophilic through membrane transporter proteins such as P-glycoprotein, multidrug-resistance proteins MDRP1-9, ABCG2 (the breast cancer resistance protein) and organic anion transporters (OATs) present on capillary endothelial cells (Deng et al, 2018;Gil-Martins et al, 2020). Normally, BBB also prevents the transmigration of blood cells and cancer cells, however, studies suggest that the defenses of the BBB can be disrupted in the presence of brain metastases (Brosnan and Anders, 2018).…”

Section: The Brain Nichementioning

confidence: 99%

Biomimetic Microfluidic Platforms for the Assessment of Breast Cancer Metastasis

Sigdel

Gupta

Faizee

et al. 2021

Front. Bioeng. Biotechnol.

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Of around half a million women dying of breast cancer each year, more than 90% die due to metastasis. Models necessary to understand the metastatic process, particularly breast cancer cell extravasation and colonization, are currently limited and urgently needed to develop therapeutic interventions necessary to prevent breast cancer metastasis. Microfluidic approaches aim to reconstitute functional units of organs that cannot be modeled easily in traditional cell culture or animal studies by reproducing vascular networks and parenchyma on a chip in a three-dimensional, physiologically relevant in vitro system. In recent years, microfluidics models utilizing innovative biomaterials and micro-engineering technologies have shown great potential in our effort of mechanistic understanding of the breast cancer metastasis cascade by providing 3D constructs that can mimic in vivo cellular microenvironment and the ability to visualize and monitor cellular interactions in real-time. In this review, we will provide readers with a detailed discussion on the application of the most up-to-date, state-of-the-art microfluidics-based breast cancer models, with a special focus on their application in the engineering approaches to recapitulate the metastasis process, including invasion, intravasation, extravasation, breast cancer metastasis organotropism, and metastasis niche formation.

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“…This marine compound demonstrated anticancer and antioxidative stress properties [ 80 ], but also anti-cholinesterase activity and induction of P-gp expression and activity [ 59 ]. P-gp, an important member of the ATP-binding cassette transporter superfamily, is related with AD once is an efflux transporter associated with Aβ transport out of the brain [ 81 ], and there is evidence that increased levels of P-gp result in and increased amyloid-β clearance [ 59 ]. These properties suggest that fascaplysin should be investigated as a therapeutic for AD.…”

Section: Marine Natural Productsmentioning

confidence: 99%

Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer’s Disease

et al. 2020

Self Cite

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Alzheimer’s disease (AD) is a multifactorial disease characterized by the presence of amyloid plaques, neurofibrillary tangles, and nerve cell death that affects, mainly, older people. After decades of investigation, the search for an efficacious treatment for AD remains and several strategies can be and are being employed in this journey. In this review, four of the most promising strategies, alongside with its most promising agents under investigation or development are highlighted. Marine natural products (MNP) are a source of unique chemical structures with useful biological activities for AD treatment. One of the most promising compounds, a marine-derived acidic oligosaccharide (GV-971) just passed phase III clinical trials with a unique mechanism of action. Combination therapy and multitargeted-directed ligand therapy (MTDL) are also two important strategies, with several examples in clinical trials, based on the belief that the best approach for AD is a therapy capable of modulating multiple target pathways. Drug repurposing, a strategy that requires a smaller investment and is less time consuming, is emerging as a strong contender with a variety of pharmacological agents resurfacing in an attempt to identify a therapeutic candidate capable of modifying the course of this disease.

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

Cited by 104 publications

References 335 publications

Role of ABCA7 in Human Health and in Alzheimer’s Disease

Role of ABCA7 in Human Health and in Alzheimer’s Disease

Biomimetic Microfluidic Platforms for the Assessment of Breast Cancer Metastasis

Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer’s Disease

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