Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary

Bernstein, Hans‐Gert; Hölzl, Gloria; Dobrowolny, Henrik; Hildebrandt, Jens; Trübner, Kurt; Krohn, Markus; Bogerts, Bernhard; Pahnke, Jens

doi:10.1016/j.mad.2014.08.003

Cited by 42 publications

(33 citation statements)

References 61 publications

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“…Yet another—less explored—possibility is that the ABCB1 and CYP2D6 polymorphisms are also related to pharmacodynamic effects. According to a recent publication, in addition to BBB, P‐gp is expressed in parenchymal central nervous system cells including neurons (Bernstein et al, ). There is also published information available indicating that, in the plasma membrane, P‐gp interacts physically and functionally with caveolin‐1 (Cav‐1), another membrane protein that is important for synaptic signalling, dendritic arborization, and neuronal survival (Lee et al, ).…”

Section: Discussionmentioning

confidence: 99%

ABCB1 and CYP2D6 polymorphisms and treatment response of psychotic patients in a naturalistic setting

Papazisis

Goulas

Sarrigiannidis

et al. 2017

Human Psychopharmacology

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Objectives: The aim of our study was to examine the association between ABCB1 polymorphisms G2677T/A (rs2032582) and C3435T (rs1045642) and common CYP2D6 variants, with the response to antipsychotic treatment of psychotic patients, in a naturalistic setting, in Greece.Methods: One hundred patients suffering from schizophrenia and other psychotic disorders were included in the study. Dosages were normalized to chlorpromazine equivalents. Response following 1 month of treatment was assessed as either a continuous variable, using the distribution of the corrected Positive and Negative Syndrome Scale percent change, or as a dichotomous variable defined as the number of patients scoring ≥30% from the corrected baseline Positive and Negative Syndrome Scale score. Genotyping was achieved with established polymerase chain reaction-restriction fragment length polymorphism methods.Results: With response treated as a continuous variable, the homozygous recessive rs2032582 genotypes (TT) who were simultaneously carriers of a loss-of-function CYP2D6 allele (*4 or *5) responded significantly worse than the rest of the patients. Comparison of genotype frequencies revealed a statistically significant association of the above combination. No significant association between chlorpromazine equivalents and the tested genotypes was detected. Conclusion:We have detected a possible interaction between ABCB1 and CYP2D6 in affecting response of psychotic patients to drug treatment, in a naturalistic setting.

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Section: Discussionmentioning

confidence: 99%

ABCB1 and CYP2D6 polymorphisms and treatment response of psychotic patients in a naturalistic setting

Papazisis

Goulas

Sarrigiannidis

et al. 2017

Human Psychopharmacology

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“…Due the contribution of ABC transporters on Aβ clearance in AD, they have been proposed as potential therapeutic targets (Krohn et al, 2011). Moreover, ABCB1 dysfunction has been also associated with other neurodegenerative disorders such as PD, progressive supranuclear palsy (PSP) or genetically associated with depressive disorders (Bernstein et al, 2014). As most of these efflux pumps are up-regulated by Nrf2, using Nrf2 activators may provide an important tool to increase the activity of ABC transporters.…”

Section: Abc Transportersmentioning

confidence: 99%

Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function

Esteras¹,

Dinkova‐Kostova²,

Abramov³

2016

Biological Chemistry

143

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Abstract:The nuclear factor erythroid-derived 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor wellknown for its function in controlling the basal and inducible expression of a variety of antioxidant and detoxifying enzymes. As part of its cytoprotective activity, increasing evidence supports its role in metabolism and mitochondrial bioenergetics and function. Neurodegenerative diseases are excellent candidates for Nrf2-targeted treatments. Most neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Friedreich's ataxia are characterized by oxidative stress, misfolded protein aggregates, and chronic inflammation, the common targets of Nrf2 therapeutic strategies. Together with them, mitochondrial dysfunction is implicated in the pathogenesis of most neurodegenerative disorders. The recently recognized ability of Nrf2 to regulate intermediary metabolism and mitochondrial function makes Nrf2 activation an attractive and comprehensive strategy for the treatment of neurodegenerative disorders. This review aims to focus on the potential therapeutic role of Nrf2 activation in neurodegeneration, with special emphasis on mitochondrial bioenergetics and function, metabolism and the role of transporters, all of which collectively contribute to the cytoprotective activity of this transcription factor.

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“…Furthermore, several anticancer drugs such as camptothecins, epipodophyllotoxins, and certain tyrosine kinase inhibitors (TKIs) are recognized by all three ABC transporters (sharing substrate range). Hence, the sole inhibition or downregulation of one transporter can be compensated by the upregulation of another . Moreover, it was recently shown that these transporters might be simultaneously expressed, which extends the cross‐resistance of cancer cells regarding used antineoplastic agents (differing substrate range).…”

Section: Introductionmentioning

confidence: 99%

“…and HL60/R-CP164 ),6-mercaptopurine (T-ALL165 ) methotrexate (CEM/MTX166,167 ), mitoxantrone (DON/MX0.004-0.016168 ), or6-thioguanin (T-ALL 165 )Anti-inflammatory and antipyretic agents. The nonsteroidal anti-inflammatory drug sulindac, a reverser of MRP1mediated MDR,169 had also the ability to increase MRP1 gene expression (amongst other transporters) in HT29 human colon carcinoma cells 170.…”

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confidence: 99%

The A‐B‐C of small‐molecule ABC transport protein modulators: From inhibition to activation—a case study of multidrug resistance‐associated protein 1 (ABCC1)

Wiese

Stefan

2019

Medicinal Research Reviews

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Several mechanisms of pharmacokinetic, metabolic, and regulatory nature have been elucidated to take part or act in concert in the phenomenon of multidrug resistance (MDR). MDR is characterized by cross‐resistance of cells against chemotherapeutic agents, which are used for treatment of e.g., cancer, bacterial infections, or human immunodeficiency virus (HIV) infections. One group of proteins that combines all three stated aspects—the metabolism and distribution of drugs as well as their own regulation—is adenosine triphosphate‐binding cassette (ABC) transporters. These efflux pumps use the energy of adenosine triphosphate hydrolysis for drug translocation from the membrane and the cytosol to the extracellular space, often with cotransport of a cosubstrate. Multidrug resistance‐associated protein 1 (MRP1, ABCC1) had been discovered as one major key player in cancer‐related MDR. The xenobiotic substrates include anthracyclines, vinca alkaloids, podophyllotoxins, as well as glutathione (GSH)‐adducts of certain cytostatics. Contrary to other transport proteins involved in cancer‐related MDR the activity of MRP1 is related to the GSH content of cells. A modern strategy to overcome MRP1‐associated MDR is besides its inhibition the activation of GSH efflux, enforcing cell death due to cellular stress. In addition, it has recently been found that MRP1 contributes to the β‐amyloid protein clearance in Alzheimer's disease (AD). Collectively, transport activation of MRP1 is of therapeutic value, and furthermore helps to elucidate the transport protein function and the mechanisms behind it. This review is meant to summarize the known concepts of MRP1 activation, which might contribute to a further understanding of MRP1 in particular and ABC transporters in general.

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Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary

Cited by 42 publications

References 61 publications

ABCB1 and CYP2D6 polymorphisms and treatment response of psychotic patients in a naturalistic setting

ABCB1 and CYP2D6 polymorphisms and treatment response of psychotic patients in a naturalistic setting

Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function

The A‐B‐C of small‐molecule ABC transport protein modulators: From inhibition to activation—a case study of multidrug resistance‐associated protein 1 (ABCC1)

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