کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8479416 | 1551319 | 2008 | 18 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
2,3-Benzodiazepine-type AMPA receptor antagonists and their neuroprotective effects
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کلمات کلیدی
EAEPKCN-methyl-d-aspartateNMDAOGDMPTPNBQX1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamideABPTARPpKaAMPAPICK1NTDNARPPepAMCA1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine - 1-methyl-4-phenyl-1،2،3،6-tetrahydropyridine2,3-benzodiazepines - 2،3-بنزودیازپین هاOPCs - OPC هاexperimental autoimmune encephalomyelitis - آنسفالومیلیت خودایمنی تجربیNeurodegenerative disorders - اختلالات نوروژنیکalpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid - اسید آلفا آمینو 3-هیدروکسی-5-متیل-4-ایزوکسول پپونیکlong-term depression - افسردگی طولانی مدتCerebral ischemia - ایسکمی مغزیParkinson's disease - بیماری پارکینسونlong-term potentiation - تقویت درازمدتLTP - تقویت طولانی مدت یا LTP PDZ domain - دامنه PDZamino terminal domain - دامنه ترمینال آمینmiddle cerebral artery - شریان مغزی میانیPeriventricular leukomalacia - لکو مالاتیا پریوژنیکالNeuroprotection - محافظت نورونی یا محافظت از عصبLTD - محدودOxygen-glucose deprivation - محرومیت گلوکز اکسیژنPVL - مقاله از استخراج اجباریglutamate receptor interacting protein - پروتئین تعامل گیرنده گلوتاماتsynapse-associated protein - پروتئین مرتبط با سیناپسProtein kinase-C - پروتئین کیناز CProtein kinase-A - پروتئین کیناز-ASpreading depression - گسترش افسردگیAMPA receptors - گیرنده های AMPA
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
AMPA receptors are fast ligand-gated members of glutamate receptors in neuronal and many types of non-neuronal cells. The heterotetramer complexes are assembled from four subunits (GluR1-4) in region-, development- and function-selective patterns. Each subunit contains three extracellular domains (a large amino terminal domain, an agonist-binding domain and a transducer domain), and three transmembrane segments with a loop (pore forming domain), as well as the intracellular carboxy terminal tail (traffic and conductance regulatory domain). The binding of the agonist (excitatory amino acids and their derivatives) initiates conformational realignments, which transmit to the transducer domain and membrane spanning segments to gate the channel permeable to Na+, K+ and more or less to Ca2+. Several 2,3-benzodiazepines act as non-competitive antagonists of the AMPA receptor (termed also negative allosteric modulators), which are thought to bind to the transducer domains and inhibit channel gating. Analysing their effects in vitro, it has been possible to recognize a structure-activity relationship, and to describe the critical parts of the molecules involved in their action at AMPA receptors. Blockade of AMPA receptors can protect the brain from apoptotic and necrotic cell death by preventing neuronal excitotoxicity during pathophysiological activation of glutamatergic neurons. Animal experiments provided evidence for the potential usefulness of non-competitive AMPA antagonists in the treatment of human ischemic and neurodegenerative disorders including stroke, multiple sclerosis, Parkinson's disease, periventricular leukomalacia and motoneuron disease. 2,3-Benzodiazepine AMPA antagonists can protect against seizures, decrease levodopa-induced dyskinesia in animal models of Parkinson's disease demonstrating their utility for the treatment of a variety of CNS disorders.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 52, Issues 1â2, January 2008, Pages 166-183
Journal: Neurochemistry International - Volume 52, Issues 1â2, January 2008, Pages 166-183
نویسندگان
Gábor Szénási, Miklos Vegh, Geza Szabo, Szabolcs Kertesz, Gabor Kapus, Mihaly Albert, Zoltan Greff, Istvan Ling, Jozsef Barkoczy, Gyula Simig, Michael Spedding, Laszlo G. Jr.,