Abstract:
:The blood-brain barrier is a natural diffusion barrier, which expresses active carriers extruding drugs on their way to the brain back into the blood against concentration gradients. Whereas these so-called adenosine triphosphate-binding cassette (ABC) transporters prevent the brain entry of toxic compounds under physiological conditions, they complicate pharmacotherapies in neurological disease. Recent observations in animal models of ischemic stroke, drug-resistant epilepsy, and brain cancer showed that the prototype of ABC transporters, ABCB1, is upregulated on brain injury, deactivation of this carrier considerably enhancing the accumulation of neuroprotective, antiepileptic, and chemotherapeutic compounds. These studies provide the proof of concept that the efficacy of brain-targeting drugs may significantly be improved when drug efflux is blocked. Under clinical conditions, efforts currently are made to enhance drug accumulation by selecting new compounds that do not bind to efflux carriers or deactivating ABC transporters by targeted downregulation or pharmacological inhibition. We predict that strategies aiming at circumventing drug efflux may greatly facilitate progress in neurological therapies.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Hermann DM,Kilic E,Spudich A,Krämer SD,Wunderli-Allenspach H,Bassetti CLdoi
10.1002/ana.21012subject
Has Abstractpub_date
2006-11-01 00:00:00pages
489-98issue
5eissn
0364-5134issn
1531-8249journal_volume
60pub_type
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journal_title:Annals of neurology
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journal_title:Annals of neurology
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abstract::Six polypeptides resolved by two-dimensional electrophoresis of homogenates from human skeletal muscle have been identified as tropomyosin by electrophoretic and immunochemical methods. The 6 proteins are consistently present in approximately the same abundance in normal biceps, deltoid, gastrocnemius, and quadriceps ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410180211
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410070608
更新日期:1980-06-01 00:00:00
abstract::The duration of the antiparkinsonian action of levodopa was studied in 48 patients with various response patterns to the oral administration of the dopamine precursor. Deterioration in motor scores after abrupt cessation of a steady-state intravenous levodopa infusion occurred at two successive rates: an initial rapid...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410240303
更新日期:1988-09-01 00:00:00
abstract::We report the clinical and neuropathological findings in an immunocompetent 19-year-old patient with a fatal acute Epstein-Barr virus (EBV) meningoencephalitis and a lymphoma-like B-lymphocyte response. Our results suggest that an immunotoxic rather than direct viral neuronal invasion mediates brain damage in EBV ence...
journal_title:Annals of neurology
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abstract::The development of serotonin (5HT1B/1D) agonists as treatments for the acute attack of migraine has resulted in considerable interest in their mechanism of action and, to some extent, renewed interest in the role of serotonin (5-hydroxytryptamine; 5HT) in the disorder. The initial synthesis of this class of compounds ...
journal_title:Annals of neurology
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doi:10.1002/ana.410430605
更新日期:1998-06-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.21465
更新日期:2008-09-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410120308
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410030609
更新日期:1978-06-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410060508
更新日期:1979-11-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410340306
更新日期:1993-09-01 00:00:00
abstract::One of the most striking manifestations of Down's syndrome is profound mental retardation. Furthermore, after 35 years of age, many patients with Down's syndrome develop clinical and pathological features of Alzheimer's disease. Since brains of patients with Alzheimer's disease show significant loss of neurons in the ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410180306
更新日期:1985-09-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.1140
更新日期:2001-09-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410430514
更新日期:1998-05-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.23653
更新日期:2012-10-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.23951
更新日期:2013-09-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410260204
更新日期:1989-08-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410110506
更新日期:1982-05-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410320502
更新日期:1992-11-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410440518
更新日期:1998-11-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2015-10-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200407
更新日期:1986-10-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24169
更新日期:2014-05-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20548
更新日期:2005-08-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.23577
更新日期:2012-08-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150608
更新日期:1984-06-01 00:00:00
abstract::Persons affected with tuberous sclerosis complex (TSC) develop a wide range of neurological abnormalities including aberrant neuronal migration and seizures. In an effort to model TSC-associated central nervous system abnormalities in mice, we generated two independent lines of astrocyte-specific Tsc1 conditional knoc...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10283
更新日期:2002-09-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150214
更新日期:1984-02-01 00:00:00
abstract::We carried out a comprehensive assessment of eye movements in 2 subjects with impaired facial learning and recognition to determine if the defect might be associated with abnormal scanning of faces. Standard electroculogram showed that fixation, pursuit, saccades, and scanning of salient features of scenes and faces w...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410220111
更新日期:1987-07-01 00:00:00