Allosteric Modulation of an Excitatory Amino Acid Transporter: The Subtype-Selective Inhibitor UCPH-101 Exerts Sustained Inhibition of EAAT1 through an Intramonomeric Site in the Trimerization Domain
نویسندگان
چکیده
منابع مشابه
Allosteric modulation of an excitatory amino acid transporter: the subtype-selective inhibitor UCPH-101 exerts sustained inhibition of EAAT1 through an intramonomeric site in the trimerization domain.
In the present study, the mechanism of action and molecular basis for the activity of the first class of selective inhibitors of the human excitatory amino acid transporter subtype 1 (EAAT1) and its rodent ortholog GLAST are elucidated. The previously reported specificity of UCPH-101 and UCPH-102 for EAAT1 over EAAT2 and EAAT3 is demonstrated to extend to the EAAT4 and EAAT5 subtypes as well. I...
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Although the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH-101 has become a standard pharmacological tool compound for in vitro and ex vivo studies in the EAAT research field, its inability to penetrate the blood-brain barrier makes it unsuitable for in vivo studies. In the present study, per os (p.o.) administration (40 mg kg(-1) ) of the closely related analogue...
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Human members of the solute carrier 1 (SLC1) family of transporters take up excitatory neurotransmitters in the brain and amino acids in peripheral organs. Dysregulation of the function of SLC1 transporters is associated with neurodegenerative disorders and cancer. Here we present crystal structures of a thermostabilized human SLC1 transporter, the excitatory amino acid transporter 1 (EAAT1), w...
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چکیده ندارد.
15 صفحه اولAberrant expression of the glutamate transporter excitatory amino acid transporter 1 (EAAT1) in Alzheimer's disease.
Glutamate-mediated toxicity has been implicated in the neurodegeneration observed in Alzheimer's disease. In particular, glutamate transport dysfunction may increase susceptibility to glutamate toxicity, thereby contributing to neuronal cell injury and death. In this study, we examined the cellular localization of the glial glutamate transporter excitatory amino acid transporter 1 (EAAT1) in th...
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ژورنال
عنوان ژورنال: Journal of Neuroscience
سال: 2013
ISSN: 0270-6474,1529-2401
DOI: 10.1523/jneurosci.3396-12.2013