Role of Excitatory Amino Acid Transporter‐2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics
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Cites background from "Role of Excitatory Amino Acid Trans..."
...…L-glu and L-asp clearance should dampen the excitotoxic component of these diseases, many researchers have set out to identify compounds that induce EAAT2, which is the principal EAAT in the brain and most frequently found to be downregulated (Sheldon and Robinson, 2007; Kim et al., 2011)....
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References
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Additional excerpts
...NF-kB is primarily a transcriptional activator (Baldwin, 1996)....
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2,482 citations
"Role of Excitatory Amino Acid Trans..." refers background in this paper
...The human EAAT2 promoter was significantly activated by CEF, amoxicillin and dibutyryl cyclic AMP while controls such as glutamate and glycine had no effect (Rothstein et al., 2005)....
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...We have identified b-lactam antibiotics, such as CEF, as transcriptional activators of EAAT2 that are capable of providing neuronal protection through facilitating glutamate uptake by astroglial cells (Rothstein et al., 2005)....
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...CEF also altered cellular neurodegeneration in vivo and G93A mice receiving CEF at 70 days of age showed a significant prevention of motor neuron loss and reduction JOURNAL OF CELLULAR PHYSIOLOGY of hypercellular gliosis compared to control mice (Rothstein et al., 2005)....
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...…A N D G L U T A M A T E I N N E U R O D E G E N E R A T I O N 2489 Biochemically, glutamate transport activity was enhanced by treatment with cephalosporin, one of the derivatives of CEF, as evidenced by increased glutamate uptake into the cortical membrane or spinal cord (Rothstein et al., 2005)....
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...…of compounds identifies b-lactam antibiotics as inducers of EAAT2 Administration of 1,040 FDA-approved drugs and nutritionals to spinal cord slice cultures derived from 9-day-old rats identified compounds that increased activity of EAAT2 and the levels of EAAT2 protein (Rothstein et al., 2005)....
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2,478 citations
"Role of Excitatory Amino Acid Trans..." refers background in this paper
...Additionally, NO reacts with O 2 , producing peroxynitrite (OONO ) leading to neuron damage (Lipton et al., 1993; Yamauchi et al., 1998)....
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2,095 citations
"Role of Excitatory Amino Acid Trans..." refers background in this paper
...Rats that received optimal doses of CEF displayed attenuation of cue-induced relapse to cocaineseeking behavior due to an increase in GLT1 expression in both prefrontal cortex and nucleus accumbens (Sari et al., 2009)....
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1,700 citations
"Role of Excitatory Amino Acid Trans..." refers background in this paper
...A number of neurodegenerative diseases demonstrate a level of misfolded protein accumulation including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis (ALS; Kopito and Ron, 2000; Taylor et al., 2002)....
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