A Medicinal Chemistry Perspective on Excitatory Amino Acid Transporter 2 Dysfunction in Neurodegenerative Diseases

Trafficking of the glutamate transporter is impaired in LRRK2-related Parkinson’s disease

(2022) Ludovica Iovino et al.   ACTA NEUROPATHOLOGICA

Extracellular tau oligomers affect extracellular glutamate handling by astrocytes through downregulation of GLT‐1 expression and impairment of NKA1A2 function

(2022) Domenica Donatella Li Puma et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Structural basis of ligand binding modes of human EAAT2

(2022) Zhenglai Zhang et al.   Nature Communications

Structural insights into inhibitory mechanism of human excitatory amino acid transporter EAAT2

(2022) Takafumi Kato et al.   Nature Communications

EAAT2 as a therapeutic research target in Alzheimer's disease: A systematic review

(2022) Oliver W. G. Wood et al.   Frontiers in Neuroscience

Effect of Subthalamic Stimulation and Electrode Implantation in the Striatal Microenvironment in a Parkinson’s Disease Rat Model

(2022) Ana Carolina Pinheiro Campos et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Design and Characterization of Novel Small Molecule Activators of Excitatory Amino Acid Transporter 2

(2022) Sanjay Das et al.   ACS Medicinal Chemistry Letters

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds

(2022) Antonio Shegani et al.   Chemical Reviews

Metabolism of [1,6‐ 13 C]glucose in the cerebellum of 18‐day old rats: Comparison with cerebral metabolism

(2021) Gustavo C. Ferreira et al.   JOURNAL OF NEUROCHEMISTRY

Reactive astrocyte nomenclature, definitions, and future directions

(2021) Carole Escartin et al.   NATURE NEUROSCIENCE

Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport

(2021) Biao Qiu et al.   Science Advances

Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer’s disease

(2021) Dawn C Matthews et al.   BRAIN

Ceftriaxone regulates glutamate production and vesicular assembly in presynaptic terminals through GLT-1 in APP/PS1 mice

(2021) ShuJuan Fan et al.   NEUROBIOLOGY OF LEARNING AND MEMORY

Systematic review of human post‐mortem immunohistochemical studies and bioinformatics analyses unveil the complexity of astrocyte reaction in Alzheimer's disease

(2021) Lucía Viejo et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

EAAT2 Expression in the Hippocampus, Subiculum, Entorhinal Cortex and Superior Temporal Gyrus in Alzheimer’s Disease

(2021) Jason H. Y. Yeung et al.   Frontiers in Cellular Neuroscience

Exercise increases striatal Glu reuptake and improves motor dysfunction in 6-OHDA-induced Parkinson’s disease rats

(2021) Yan Feng et al.   EXPERIMENTAL BRAIN RESEARCH

Induction of Parkinsonian-Like Changes via Targeted Downregulation of Astrocytic Glutamate Transporter GLT-1 in the Striatum

(2021) Chao Ren et al.   Journal of Parkinsons Disease

Generation of a Novel Mouse Model of Parkinson’s Disease via Targeted Knockdown of Glutamate Transporter GLT-1 in the Substantia Nigra

(2020) Yunlong Zhang et al.   ACS Chemical Neuroscience

A computational approach yields selective inhibitors of human excitatory amino acid transporter 2 (EAAT2)

(2020) Kelly L Damm-Ganamet et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Elucidation of the Structure and Synthesis of Neuroprotective Low Molecular Mass Components of the Parawixia bistriata Spider Venom

(2020) Yvonne M. Forster et al.   ACS Chemical Neuroscience

Amyloid‐β oligomers in cellular models of Alzheimer’s disease

(2020) Igor C. Fontana et al.   JOURNAL OF NEUROCHEMISTRY

Erythrocytic α-synuclein contained in microvesicles regulates astrocytic glutamate homeostasis: a new perspective on Parkinson’s disease pathogenesis

(2020) Lifu Sheng et al.   Acta Neuropathologica Communications

Novel Positive Allosteric Modulators of Glutamate Transport Have Neuroprotective Properties in an in Vitro Excitotoxic Model

(2019) Romulo Martelli Falcucci et al.   ACS Chemical Neuroscience

Membralin deficiency dysregulates astrocytic glutamate homeostasis, leading to ALS-like impairment

(2019) Lu-Lin Jiang et al.   JOURNAL OF CLINICAL INVESTIGATION

Neuropsychiatric Symptoms as Predictors of Clinical Course in Neurodegeneration. A Longitudinal Study

(2019) José Manuel Santacruz Escudero et al.   Frontiers in Aging Neuroscience

Imidazoline 2 binding sites reflecting astroglia pathology in Parkinson’s disease: an in vivo11C-BU99008 PET study

(2019) Heather Wilson et al.   BRAIN

Cognitive, Emotional and Psychological Manifestations in Amyotrophic Lateral Sclerosis at Baseline and Overtime: A Review

(2019) Soumia Benbrika et al.   Frontiers in Neuroscience

Divergent roles of astrocytic versus neuronal EAAT2 deficiency on cognition and overlap with aging and Alzheimer’s molecular signatures

(2019) Abhijeet Sharma et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Wnt1 Promotes EAAT2 Expression and Mediates the Protective Effects of Astrocytes on Dopaminergic Cells in Parkinson’s Disease

(2019) Lei Wei et al.   NEURAL PLASTICITY

Effect of ceftriaxone on paired-pulse response and long-term potentiation of hippocampal dentate gyrus neurons in rats with Alzheimer-like disease

(2019) Nasrin Hamidi et al.   LIFE SCIENCES

NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease

(2018) Clifford R. Jack et al.   Alzheimers & Dementia

Chemoenzymatic synthesis and pharmacological characterization of functionalized aspartate analogues as novel excitatory amino acid transporter inhibitors

(2018) Haigen Fu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Laquinimod ameliorates excitotoxic damage by regulating glutamate re-uptake

(2018) Antonietta Gentile et al.   Journal of Neuroinflammation

Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes

(2018) Johnny Habchi et al.   Nature Chemistry

Glutamatergic Signaling in the Central Nervous System: Ionotropic and Metabotropic Receptors in Concert

(2018) Andreas Reiner et al.   NEURON

Novel interaction between Alzheimer’s disease-related protein presenilin 1 and glutamate transporter 1

(2018) Katarzyna Marta Zoltowska et al.   Scientific Reports

Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain

(2018) Eiji Kobayashi et al.   Scientific Reports

Glutamate Transporter GLT1 Expression in Alzheimer Disease and Dementia With Lewy Bodies

(2018) Paula Garcia-Esparcia et al.   Frontiers in Aging Neuroscience

Region- and Age-Specific Changes in Glutamate Transport in the AβPP23 Mouse Model for Alzheimer's Disease

(2018) Anneleen Schallier et al.   JOURNAL OF ALZHEIMERS DISEASE

GLT-1 Loss Accelerates Cognitive Deficit Onset in an Alzheimer's Disease Animal Model

(2018) Paramita Mookherjee et al.   JOURNAL OF ALZHEIMERS DISEASE

Innate immune alterations are elicited in microglial cells before plaque deposition in the Alzheimer’s disease mouse model 5xFAD

(2018) Antonio Boza-Serrano et al.   Scientific Reports

Sulbactam Protects Hippocampal Neurons Against Oxygen-Glucose Deprivation by Up-Regulating Astrocytic GLT-1 via p38 MAPK Signal Pathway

(2018) Jie Qi et al.   Frontiers in Molecular Neuroscience

Ceftriaxone Improves Cognitive Function and Upregulates GLT-1-Related Glutamate-Glutamine Cycle in APP/PS1 Mice

(2018) ShuJuan Fan et al.   JOURNAL OF ALZHEIMERS DISEASE

Alzheimer's disease

(2017) C. A. Lane et al.   EUROPEAN JOURNAL OF NEUROLOGY

Mutation of the caspase-3 cleavage site in the astroglial glutamate transporter EAAT2 delays disease progression and extends lifespan in the SOD1-G93A mouse model of ALS

(2017) Lauren Taylor Rosenblum et al.   EXPERIMENTAL NEUROLOGY

Amyloid-beta peptide decreases expression and function of glutamate transporters in nervous system cells

(2017) Huichun Tong et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

ALS genetic epidemiology ‘How simplex is the genetic epidemiology of ALS?’

(2017) Jan H Veldink   JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

Calcineurin/NFAT Signaling in Activated Astrocytes Drives Network Hyperexcitability in Aβ-Bearing Mice

(2017) Pradoldej Sompol et al.   JOURNAL OF NEUROSCIENCE

Amyotrophic lateral sclerosis

(2017) Michael A van Es et al.   LANCET

Ceftriaxone reduces L -dopa-induced dyskinesia severity in 6-hydroxydopamine parkinson's disease model

(2017) Tanya Chotibut et al.   MOVEMENT DISORDERS

ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles

(2017) Roberta Bonafede et al.   Frontiers in Cellular Neuroscience

Involvement of Astrocytes in Alzheimer’s Disease from a Neuroinflammatory and Oxidative Stress Perspective

(2017) Rodrigo E. González-Reyes et al.   Frontiers in Molecular Neuroscience

Concise Asymmetric Synthesis and Pharmacological Characterization of All Stereoisomers of Glutamate Transporter Inhibitor TFB-TBOA and Synthesis of EAAT Photoaffinity Probes

(2016) Michele Leuenberger et al.   ACS Chemical Neuroscience

Central Nervous System Multiparameter Optimization Desirability: Application in Drug Discovery

(2016) Travis T. Wager et al.   ACS Chemical Neuroscience

β-Sulfonamido Functionalized Aspartate Analogues as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype Selectivity Profiles Arising from Subtle Structural Differences

(2016) Jacob C. Hansen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Neuroprotective Effects of the Glutamate Transporter Activator (R)-(−)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153) following Traumatic Brain Injury in the Adult Rat

(2016) Andréia Cristina Karklin Fontana et al.   JOURNAL OF NEUROTRAUMA

Alzheimer’s disease-like APP processing in wild-type mice identifies synaptic defects as initial steps of disease progression

(2016) Mickael Audrain et al.   Molecular Neurodegeneration

GLT-1: The elusive presynaptic glutamate transporter

(2016) Theresa S. Rimmele et al.   NEUROCHEMISTRY INTERNATIONAL

Mapping synaptic glutamate transporter dysfunction in vivo to regions surrounding Aβ plaques by iGluSnFR two-photon imaging

(2016) J. K. Hefendehl et al.   Nature Communications

Prevalence of Amyloid PET Positivity in Dementia Syndromes

(2015) Rik Ossenkoppele et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Restored glial glutamate transporter EAAT2 function as a potential therapeutic approach for Alzheimer’s disease

(2015) Kou Takahashi et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Molecular determinants of transport stimulation of EAAT2 are located at interface between the trimerization and substrate transport domains

(2015) Ole V. Mortensen et al.   JOURNAL OF NEUROCHEMISTRY

Current approaches to enhance glutamate transporter function and expression

(2015) Andréia C. K. Fontana   JOURNAL OF NEUROCHEMISTRY

Differential Regulation of Two Isoforms of the Glial Glutamate Transporter EAAT2 by DLG1 and CaMKII

(2015) S. M. Underhill et al.   JOURNAL OF NEUROSCIENCE

Effects of (R)-(−)-5-methyl-1-nicotinoyl-2-pyrazoline on glutamate transporter 1 and cysteine/glutamate exchanger as well as ethanol drinking behavior in male, alcohol-preferring rats

(2015) Munaf Aal-Aaboda et al.   JOURNAL OF NEUROSCIENCE RESEARCH

Mechanism of raloxifene-induced upregulation of glutamate transporters in rat primary astrocytes

(2014) Pratap Karki et al.   GLIA

Small-molecule activator of glutamate transporter EAAT2 translation provides neuroprotection

(2014) Qiongman Kong et al.   JOURNAL OF CLINICAL INVESTIGATION

Development of Purine-Derived 18F-Labeled Pro-drug Tracers for Imaging of MRP1 Activity with PET

(2014) Eva Galante et al.   JOURNAL OF MEDICINAL CHEMISTRY

Extensive dysregulations of oligodendrocytic and astrocytic connexins are associated with disease progression in an amyotrophic lateral sclerosis mouse model

(2014) Yiwen Cui et al.   Journal of Neuroinflammation

How Local Excitation-Inhibition Ratio Impacts the Whole Brain Dynamics

(2014) G. Deco et al.   JOURNAL OF NEUROSCIENCE

Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial

(2014) Merit E Cudkowicz et al.   LANCET NEUROLOGY

Sulbactam Plays Neuronal Protective Effect Against Brain Ischemia via Upregulating GLT1 in Rats

(2014) Xin Cui et al.   MOLECULAR NEUROBIOLOGY

Astrocytes and Glutamate Homoeostasis in Alzheimer's Disease: A Decrease in Glutamine Synthetase, But Not in Glutamate Transporter-1, in the Prefrontal Cortex

(2013) Magdalena Kulijewicz-Nawrot et al.   ASN Neuro

cAMP Response Element-binding Protein (CREB) and Nuclear Factor κB Mediate the Tamoxifen-induced Up-regulation of Glutamate Transporter 1 (GLT-1) in Rat Astrocytes

(2013) Pratap Karki et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The GLT-1 (EAAT2; slc1a2) glutamate transporter is essential for glutamate homeostasis in the neocortex of the mouse

(2013) Lars Petter Bjørnsen et al.   JOURNAL OF NEUROCHEMISTRY

Design and Initial Results of a Multi-Phase Randomized Trial of Ceftriaxone in Amyotrophic Lateral Sclerosis

(2013) James D. Berry et al.   PLoS One

Neuropathological Alterations in Alzheimer Disease

(2013) A. Serrano-Pozo et al.   Cold Spring Harbor Perspectives in Medicine

Transforming growth factor-α mediates estrogen-induced upregulation of glutamate transporter GLT-1 in rat primary astrocytes

(2012) Eunsook Lee et al.   GLIA

Combined excitotoxic–oxidative stress and the concept of non-cell autonomous pathology of ALS: Insights into motoneuron axonopathy and astrogliosis

(2012) Nicole Wallis et al.   NEUROCHEMISTRY INTERNATIONAL

Reactive Glia not only Associates with Plaques but also Parallels Tangles in Alzheimer's Disease

(2011) Alberto Serrano-Pozo et al.   AMERICAN JOURNAL OF PATHOLOGY

Structure–activity relationship study of pyridazine derivatives as glutamate transporter EAAT2 activators

(2011) Xuechao Xing et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Riluzole elevates GLT-1 activity and levels in striatal astrocytes

(2011) Marica Carbone et al.   NEUROCHEMISTRY INTERNATIONAL

Increased RNA editing in EAAT2 pre-mRNA from amyotrophic lateral sclerosis patients: Involvement of a cryptic polyadenylation site

(2011) Rachel Flomen et al.   NEUROSCIENCE LETTERS

13C MRS studies of neuroenergetics and neurotransmitter cycling in humans

(2011) Douglas L. Rothman et al.   NMR IN BIOMEDICINE

In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington's disease subjects

(2010) M. Faideau et al.   HUMAN MOLECULAR GENETICS

Neuroprotective Drug Riluzole Amplifies the Heat Shock Factor 1 (HSF1)- and Glutamate Transporter 1 (GLT1)-dependent Cytoprotective Mechanisms for Neuronal Survival

(2010) Alice Y. C. Liu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Role of Excitatory Amino Acid Transporter-2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics

(2010) Keetae Kim et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Increased expression of cholesterol 24S-hydroxylase results in disruption of glial glutamate transporter EAAT2 association with lipid rafts: a potential role in Alzheimer’s disease

(2010) Guilian Tian et al.   JOURNAL OF NEUROCHEMISTRY

Aberrant Detergent-Insoluble Excitatory Amino Acid Transporter 2 Accumulates in Alzheimer Disease

(2010) Randall L. Woltjer et al.   JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY

Glutamate transporter variants reduce glutamate uptake in Alzheimer's disease

(2010) Heather A. Scott et al.   NEUROBIOLOGY OF AGING

New views of glutamate transporter structure and function: Advances and challenges

(2010) Jie Jiang et al.   NEUROPHARMACOLOGY

Astrogliosis in amyotrophic lateral sclerosis: Role and therapeutic potential of astrocytes

(2010) Marcelo R. Vargas et al.   Neurotherapeutics

The blood-brain barrier and glutamate

(2009) Richard A Hawkins   AMERICAN JOURNAL OF CLINICAL NUTRITION

Inhibitory effects of (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA) on the astrocytic sodium responses to glutamate

(2009) Luigi Bozzo et al.   BRAIN RESEARCH

Amitriptyline upregulates EAAT1 and EAAT2 in neuropathic pain rats

(2009) Qing-Xiang Mao et al.   BRAIN RESEARCH BULLETIN

Excitatory amino acid transporter 2 associates with phosphorylated tau and is localized in neurofibrillary tangles of tauopathic brains

(2009) Kumi Sasaki et al.   FEBS LETTERS

Variation in aggregation propensities among ALS-associated variants of SOD1: Correlation to human disease

(2009) Mercedes Prudencio et al.   HUMAN MOLECULAR GENETICS

Cognitive Decline in Alzheimer's Disease Is Associated with Selective Changes in Calcineurin/NFAT Signaling

(2009) H. M. Abdul et al.   JOURNAL OF NEUROSCIENCE

Reverse glial glutamate uptake triggers neuronal cell death through extrasynaptic NMDA receptor activation

(2009) E. Gouix et al.   MOLECULAR AND CELLULAR NEUROSCIENCE

Transport mechanism of a bacterial homologue of glutamate transporters

(2009) Nicolas Reyes et al.   NATURE

The concentrations and distributions of three C-terminal variants of the GLT1 (EAAT2; slc1a2) glutamate transporter protein in rat brain tissue suggest differential regulation

(2009) S. Holmseth et al.   NEUROSCIENCE

Chemo-Enzymatic Synthesis of (2S,4R)-2-Amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic Acid: A Novel Selective Inhibitor of Human Excitatory Amino Acid Transporter Subtype 2

(2008) Emanuelle Sagot et al.   JOURNAL OF MEDICINAL CHEMISTRY

Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1

(2007) Elena Fumagalli et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Effects of threo-β-hydroxyaspartate derivatives on excitatory amino acid transporters (EAAT4 and EAAT5)

(2003) Yasushi Shigeri et al.   JOURNAL OF NEUROCHEMISTRY