scholarly journals Recent Advance in the Relationship between Excitatory Amino Acid Transporters and Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yunlong Zhang ◽  
Feng Tan ◽  
Pingyi Xu ◽  
Shaogang Qu
Keyword(s):  
Parkinson’S Disease ◽  
Amino Acid ◽  
Animal Models ◽  
Substantia Nigra ◽  
Excitatory Amino Acid ◽  
Synaptic Cleft ◽  
Dopamine Neurons ◽  
Amino Acid Transporters ◽  
Excitatory Amino Acid Transporters ◽  
And Function

Parkinson’s disease (PD) is the most common movement disorder disease in the elderly and is characterized by degeneration of dopamine neurons and formation of Lewy bodies. Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). If glutamate is not removed promptly in the synaptic cleft, it will excessively stimulate the glutamate receptors and induce excitotoxic effects on the CNS. With lack of extracellular enzyme to decompose glutamate, glutamate uptake in the synaptic cleft is mainly achieved by the excitatory amino acid transporters (EAATs, also known as high-affinity glutamate transporters). Current studies have confirmed that decreased expression and function of EAATs appear in PD animal models. Moreover, single unilateral administration of EAATs inhibitor in the substantia nigra mimics several PD features and this is a solid evidence supporting that decreased EAATs contribute to the process of PD. Drugs or treatments promoting the expression and function of EAATs are shown to attenuate dopamine neurons death in the substantia nigra and striatum, ameliorate the behavior disorder, and improve cognitive abilities in PD animal models. EAATs are potential effective drug targets in treatment of PD and thus study of relationship between EAATs and PD has predominant medical significance currently.

Progressive Parkinsonism by acute dysfunction of excitatory amino acid transporters in the rat substantia nigra

2014 ◽  
Vol 65 ◽  
pp. 69-81 ◽  
Author(s):  
Maxime Assous ◽  
Laurence Had-Aissouni ◽  
Paolo Gubellini ◽  
Christophe Melon ◽  
Imane Nafia ◽  
...  
Keyword(s):  
Amino Acid ◽  
Substantia Nigra ◽  
Excitatory Amino Acid ◽  
Amino Acid Transporters ◽  
Excitatory Amino Acid Transporters ◽  
Rat Substantia Nigra

scholarly journals Modeling of excitatory amino acid transporters and clearance of synaptic cleft on millisecond time scale

2019 ◽  
Vol 14 (4) ◽  
pp. 407
Author(s):  
Denis Shchepakin ◽  
Leonid Kalachev ◽  
Michael Kavanaugh
Keyword(s):  
Amino Acid ◽  
Time Scale ◽  
Time Course ◽  
Transport Model ◽  
Excitatory Amino Acid ◽  
Synaptic Cleft ◽  
Amino Acid Transporters ◽  
Excitatory Amino Acid Transporters ◽  
Millisecond Time Scale ◽  
The Impact

Excitatory Amino Acid Transporters (EAATs) operate over wide time scales in the brain. They maintain low ambient concentrations of the primary excitatory amino acid neurotransmitter glutamate, but they also seem to play a significant role in clearing glutamate from the synaptic cleft in the millisecond time-scale process of chemical communication that occurs between neurons. The detailed kinetic mechanisms underlying glutamate uptake and clearance remain incompletely understood. In this work we used a combination of methods to model EAAT kinetics and gain insight into the impact of transport on glutamate dynamics in a general sense. We derive reliable estimates of the turnover rates of the three major EAAT subtypes expressed in the mammalian cerebral cortex. Previous studies have provided transporter kinetic estimates that vary over an order of magnitude. The values obtained in this study are consistent with estimates that suggest the unitary transporter rates are approximately 20-fold slower than the time course of glutamate in the synapse. A combined diffusion/transport model provides a possible mechanism for the apparent discrepancy.

scholarly journals Up-Regulation of the Excitatory Amino Acid Transporters EAAT1 and EAAT2 by Mammalian Target of Rapamycin

2016 ◽  
Vol 39 (6) ◽  
pp. 2492-2500 ◽  
Author(s):  
Abeer Abousaab ◽  
Nestor Luis Uzcategui ◽  
Bhaeldin Elsir ◽  
Florian Lang
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Mammalian Target Of Rapamycin ◽  
Synaptic Cleft ◽  
Target Of Rapamycin ◽  
Amino Acid Transporters ◽  
Protein Abundance ◽  
Excitatory Amino Acid Transporters ◽  
Neuronal Excitation ◽  
Electrode Voltage

Background: The excitatory amino-acid transporters EAAT1 and EAAT2 clear glutamate from the synaptic cleft and thus terminate neuronal excitation. The carriers are subject to regulation by various kinases. The EAAT3 isoform is regulated by mammalian target of rapamycin (mTOR). The present study thus explored whether mTOR influences transport by EAAT1 and/or EAAT2. Methods: cRNA encoding wild type EAAT1 (SLC1A3) or EAAT2 (SLC1A2) was injected into Xenopus oocytes without or with additional injection of cRNA encoding mTOR. Dual electrode voltage clamp was performed in order to determine electrogenic glutamate transport (IEAAT). EAAT2 protein abundance was determined utilizing chemiluminescence. Results: Appreciable IEAAT was observed in EAAT1 or EAAT2 expressing but not in water injected oocytes. IEAAT was significantly increased by coexpression of mTOR. Coexpression of mTOR increased significantly the maximal IEAAT in EAAT1 or EAAT2 expressing oocytes, without significantly modifying affinity of the carriers. Moreover, coexpression of mTOR increased significantly EAAT2 protein abundance in the cell membrane. Conclusions: The kinase mTOR up-regulates the excitatory amino acid transporters EAAT1 and EAAT2.

scholarly journals Excitatory Amino Acid Transporters of the Salamander Retina: Identification, Localization, and Function

1998 ◽  
Vol 18 (2) ◽  
pp. 698-712 ◽  
Author(s):  
Scott Eliasof ◽  
Jeffrey L. Arriza ◽  
Barbara H. Leighton ◽  
Michael P. Kavanaugh ◽  
Susan G. Amara
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Amino Acid Transporters ◽  
Excitatory Amino Acid Transporters ◽  
And Function

scholarly journals Klotho Sensitivity of the Neuronal Excitatory Amino Acid Transporters EAAT3 and EAAT4

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e70988 ◽  
Author(s):  
Ahmad Almilaji ◽  
Carlos Munoz ◽  
Tatsiana Pakladok ◽  
Ioana Alesutan ◽  
Martina Feger ◽  
...  
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Amino Acid Transporters ◽  
Excitatory Amino Acid Transporters

scholarly journals Interaction of Excitatory Amino Acid Transporters 1 – 3 (EAAT1, EAAT2, EAAT3) with N-Carbamoylglutamate and N-Acetylglutamate

2017 ◽  
Vol 43 (5) ◽  
pp. 1907-1916 ◽  
Author(s):  
Birgitta C. Burckhardt ◽  
Gerhard Burckhardt
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Hepatic Uptake ◽  
Xenopus Laevis Oocytes ◽  
Amino Acid Transporters ◽  
Synthetic Analog ◽  
Excitatory Amino Acid Transporters ◽  
Sodium Dependent ◽  
Inward Currents ◽  
Acetylglutamate Synthase

Background/Aims: Inborn deficiency of the N-acetylglutamate synthase (NAGS) impairs the urea cycle and causes neurotoxic hyperammonemia. Oral administration of N-carbamoylglutamate (NCG), a synthetic analog of N-acetylglutamate (NAG), successfully decreases plasma ammonia levels in the affected children. Due to structural similarities to glutamate, NCG may be absorbed in the intestine and taken up into the liver by excitatory amino acid transporters (EAATs). Methods: Using Xenopus laevis oocytes expressing either human EAAT1, 2, or 3, or human sodium-dependent dicarboxylate transporter 3 (NaDC3), transport-associated currents of NAG, NCG, and related dicarboxylates were assayed. Results: L-aspartate and L-glutamate produced saturable inward currents with Km values below 30 µM. Whereas NCG induced a small inward current only in EAAT3 expressing oocytes, NAG was accepted by all EAATs. With EAAT3, the NAG-induced current was sodium-dependent and saturable (Km 409 µM). Oxaloacetate was found as an additional substrate of EAAT3. In NaDC3-expressing oocytes, all dicarboxylates induced much larger inward currents than did L-aspartate and L-glutamate. Conclusion: EAAT3 may contribute to intestinal absorption and hepatic uptake of NCG. With respect to transport of amino acids and dicarboxylates, EAAT3 and NaDC3 can complement each other.

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