Article
Biochemistry & Molecular Biology
Zi Wen, Guang Xia, Chi Liang, Xinxing Wang, Junjie Huang, Lina Zhang, Dongyong Shan, Song Wu, Xu Cao
Summary: This study explored the mechanism of ferroptosis resistance in senescent chondrocytes and found that hyperactivation of ferroptosis metabolism was a prominent feature in these cells. However, senescent chondrocytes were able to survive and resist ferroptosis-induced cell death due to overexpression of the membrane protein EAAT1, which increased intracellular Glu levels and activated the glutathione system.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Multidisciplinary Sciences
Biao Qiu, Doreen Matthies, Eva Fortea, Zhiheng Yu, Olga Boudker
Summary: The study reveals the structure and operation mechanism of hEAAT3, suggesting it operates by an elevator mechanism involving three functionally independent subunits. The substrate-binding site near the cytoplasm has remarkably low affinity for the substrate, facilitating rapid substrate release and transport turnover. The mechanism of coupled uptake of sodium ions and substrate is conserved across evolutionarily distant families, augmented by coupling to protons in EAATs, and a mechanism involving a conserved glutamate residue mediates proton symport.
Article
Biochemistry & Molecular Biology
Shashank Pant, Qianyi Wu, Renae Ryan, Emad Tajkhorshid
Summary: EAATs, belonging to the SLC1A family of glutamate transporters, have been shown to activate chloride ion channels during transport. Molecular dynamics simulations in hEAAT1 reveal a chloride-conducting conformation, shedding light on the dual functionality of active transport and passive chloride permeation in human neurotransmitter transporters, a mechanism common across the SLC1A family.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Geriatrics & Gerontology
Bing Leng, Hairong Sun, Mengfan Li, Junwu Zhao, Xiaoxiao Liu, Ran Yao, Tengqun Shen, Zhenguang Li, Jinbiao Zhang
Summary: This study found that Parkinson's disease (PD) patients with rapid eye movement (REM) sleep behavior disorder (RBD) experience a greater decline in cognitive function. Blood neuroexosomal EAAT-2 levels are associated with cognitive decline in PD patients with RBD.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Editorial Material
Biochemistry & Molecular Biology
Hans O. Kalkman
Summary: Low levels of n-3 polyunsaturated fatty acids (n-3 PUFAs) and high levels of n-6 PUFAs in the blood circulation are associated with an increased risk for suicide. Clinical studies indicate that docosahexaenoic acid (DHA, a n-3 PUFA found in fish oil) displays protective effects against suicide. Activation of the transcription factor NRF2 by DHA is suggested to be the common pharmacological activity of current anti-suicidal medications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Qianyi Wu, Azman Akhter, Shashank Pant, Eunjoo Cho, Jin Xin Zhu, Alastair Garner, Tomoko Ohyama, Emad Tajkhorshid, Donald J. van Meyel, Renae M. Ryan
Summary: Glutamate is a crucial neurotransmitter in the mammalian CNS and its transport and regulation play a crucial role in maintaining proper CNS function. This study investigates the effects of specific mutations of the EAAT1 gene on CNS function and highlights the importance of ion channel and Cl- homeostasis in glia cells for the pathology of episodic ataxia type 6 (EA6). The study also identifies a novel mechanism involving ectopic Na+ leak conductance in glial cells.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Psychiatry
Samara J. Brown, Amelia M. Brown, Tertia D. Purves-Tyson, Xu-Feng Huang, Kelly A. Newell, Cynthia Shannon Weickert
Summary: This study suggests that alterations in the kynurenine pathway may contribute to the development of depression. The increased gene expression of enzymes in the kynurenine pathway indicates an activation of the kynurenic acid arm, possibly related to astrocyte response in depression. These findings point to dysfunction of the kynurenine pathway and its potential role in glutamate dysfunction in depression.
JOURNAL OF PSYCHIATRIC RESEARCH
(2022)
Article
Chemistry, Medicinal
Sanjay Das, Artem V. Trubnikov, Anton M. Novoselov, Alexander V. Kurkin, Joris Beld, Andrea Altieri, Sandhya Kortagere
Summary: Excitotoxicity in the brain is a causal factor in neurological and neurodegenerative disorders. The design and optimization of GTS467 and GTS511, activators of EAAT2 with low nanomolar efficacy, show potential for treating excitotoxicity-induced neurological disorders.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Zhenglai Zhang, Huiwen Chen, Ze Geng, Zhuoya Yu, Hang Li, Yanli Dong, Hongwei Zhang, Zhuo Huang, Juquan Jiang, Yan Zhao
Summary: In this study, cryo-EM structures of human EAAT2 in complexes with glutamate or selective inhibitor WAY-213613 were reported, providing important insights into substrate recognition and selective inhibition.
NATURE COMMUNICATIONS
(2022)
Article
Physiology
Kusumika Saha, Jae-Won Yang, Tina Hofmaier, SanthoshKannan Venkatesan, Thomas Steinkellner, Oliver Kudlacek, Sonja Sucic, Michael Freissmuth, Harald H. Sitte
Summary: This study identified the involvement of ARFGAP1 and ARF6 in the endocytosis of EAAT3, with ARFGAP1 utilizing its GAP activity and F508 to promote recycling of EAAT3. Additionally, a motif in the C-terminus of EAAT3 was found to regulate its endocytosis. These findings suggest a multifactorial regulation of EAAT3 endocytosis by ARFGAP1, highlighting the importance of the C-terminus in this process.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Kuo Du, Seh Hoon Oh, Rajesh K. Dutta, Tianai Sun, Wen-Hsuan Yang, Jen-Tsan Chi, Anna Mae Diehl
Summary: Inhibiting xCT can reduce myofibroblastic activity and induce ferroptosis in hepatic stellate cells (HSCs). However, targeting xCT inhibition specifically to myofibroblastic HSCs is crucial to effectively exploit ferroptosis as an anti-fibrotic strategy.
LIVER INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Santosh K. Panda, Do-Hyun Kim, Pritesh Desai, Patrick F. Rodrigues, Raki Sudan, Susan Gilfillan, Marina Cella, Steven J. Van Dyken, Marco Colonna
Summary: ILC2 cells selectively express the Slc7a8 gene, which plays a crucial role in maintaining cellular fitness and activation. Lack of Slc7a8 leads to reduced amino acid availability, affecting energy metabolism and signaling pathway activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Neurosciences
Peter Kovermann, Miriam Engels, Frank Mueller, Christoph Fahlke
Summary: Excitatory amino acid transporters (EAATs) play a crucial role in optimizing the temporal resolution and energy demand of excitatory synapses. In addition to their primary transport function, EAATs also function as anion channels. Recent research has shed light on the physiological and pathophysiological roles of EAAT anion channels.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Huan Huang, Yuling Chen, Na Yin, Gaojie Li, Shanshan Ye, Ling Guo, Min Feng
Summary: Regulating non-apoptotic cell death of cancer cells is a promising strategy to overcome apoptosis resistance. This study demonstrates the potential of unsaturated fatty acid liposomes to induce lipid peroxidation and non-apoptotic cell death of tumor cells, as well as reverse the immunosuppressive tumor microenvironment.
MOLECULAR PHARMACEUTICS
(2023)
Article
Clinical Neurology
Iris Alvarez-merz, Maria-dolores Munoz, Jesus M. Hernandez-guijo, Jose M. Solis
Summary: Non-excitatory amino acids (AA) can induce membrane depolarization and affect synaptic transmission during hypoxia. The mixture of L-alanine, glycine, L-glutamine, and L-serine can reliably provoke this effect. AA transporters, such as system N and alanine-serine-cysteine transporter 2 (ASCT2), may serve as therapeutic targets for brain ischemia treatment.
TRANSLATIONAL STROKE RESEARCH
(2023)