Review
Chemistry, Multidisciplinary
Erin McMoneagle, Jin Zhou, Shiyao Zhang, Weixue Huang, Sunday Solomon Josiah, Ke Ding, Yun Wang, Jinwei Zhang
Summary: Epilepsy is a neurological disorder characterized by seizures, and impaired function of the KCC2 protein has been found to contribute to its pathogenesis. Enhancing KCC2 activation and regulating its phosphorylation and transcription have shown promising results in attenuating seizure severity. Recent advances in understanding the regulatory mechanisms of KCC2 have led to the discovery of novel small molecules that modulate its activity, making it a potential therapeutic target for treating epilepsy.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Pharmacology & Pharmacy
Xiyuan Ba, Chenqiu Ran, Wenjun Guo, Jing Guo, Qian Zeng, Tao Liu, Wuping Sun, Lizu Xiao, Donglin Xiong, Yelan Huang, Changyu Jiang, Yue Hao
Summary: Continuous intrathecal infusion of oxytocin can alleviate nerve injury-induced neuropathic pain behaviors by enhancing GABA inhibitory transmission, reversing the depolarizing shift in Cl- reversal potential caused by the nerve injury, which suggests the potential therapeutic significance of continuous oxytocin administration for pain management.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Abhishek Pethe, Mira Hamze, Marina Giannaki, Bernd Heimrich, Igor Medina, Anna-Maria Hartmann, Eleni Roussa
Summary: This study investigates the effects of KCC2/NBCe1 interaction on the phosphorylation pattern and function of KCC2. The results show that KCC2 and NBCe1 interact in the mouse brain and this interaction may have pathophysiological relevance.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Rebecca Jarvis, Shu Fun Josephine Ng, Anna J. Nathanson, Ross A. Cardarelli, Krithika Abiraman, Fergus Wade, Aidan Evans-Strong, Marina P. Fernandez-Campa, Tarek Z. Deeb, Joshua L. Smalley, Tanguy Jamier, Ian K. Gurrell, Lisa McWilliams, Aarti Kawatkar, Leslie C. Conway, Qi Wang, Roland W. Burli, Nicholas J. Brandon, Iain P. Chessell, Aaron J. Goldman, Jamie L. Maguire, Stephen J. Moss
Summary: Activation of KCC2 can reduce benzodiazepine-resistant seizures and decrease associated neuronal damage.
CELL REPORTS MEDICINE
(2023)
Article
Neurosciences
Maria Antonietta Coppola, Paola Gavazzo, Ilaria Zanardi, Abraham Tettey-Matey, Antonella Liantonio, Peying Fong, Michael Pusch
Summary: ClC-6 and ClC-7 are closely related intracellular Cl-/H+ antiporters that belong to the CLC family of channels and transporters. They play important roles in regulating ionic homeostasis in late endosomes and lysosomes. While the transport function of ClC-7 requires the association with the accessory protein Ostm1, ClC-6 does not. By studying their Cl- and pH-dependence, researchers have discovered unique characteristics and functional nuances of these proteins, as well as disease-associated mutants. The findings highlight the distinct roles of ClC-6 and ClC-7 in the context of their localization, and provide insights into the mechanisms underlying diseases associated with these proteins.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Biochemical Research Methods
S. Sadia Ameen, Nane Griem-Krey, Antoine Dufour, M. Iqbal Hossain, Ashfaqul Hoque, Sharelle Sturgeon, Harshal Nandurkar, Dominik F. Draxler, Robert L. Medcalf, Mohd Aizuddin Kamaruddin, Isabelle S. Lucet, Michael G. Leeming, Dazhi Liu, Amardeep Dhillon, Jet Phey Lim, Faiza Basheer, Hong-Jian Zhu, Laita Bokhari, Carli L. Roulston, Prasad N. Paradkar, Oded Kleifeld, Andrew N. Clarkson, Petrine Wellendorph, Giuseppe D. Ciccotosto, Nicholas A. Williamson, Ching-Seng Ang, Heung-Chin Cheng
Summary: Excitotoxicity is a neuronal death process initiated by over-stimulation of glutamate receptors. Proteolytic processing of proteins, particularly by calpains, plays a critical role in this process. Our study identified key synaptic regulatory proteins as substrates of calpains, and their proteolysis contributes to neuronal death by disrupting synaptic organization and function. Blocking calpain-mediated proteolysis of Src protein showed neuroprotective effects. Our findings provide new insights into excitotoxic neuronal death mechanisms and potential targets for neuroprotection.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Neurosciences
Ru Liu, Yue Xing, Herui Zhang, Junling Wang, Huanling Lai, Lipeng Cheng, Donghong Li, Tao Yu, Xiaoming Yan, Cuiping Xu, Yueshan Piao, Linghui Zeng, Horace H. Loh, Guojun Zhang, Xiaofeng Yang
Summary: Imbalanced expression of NKCC1 and KCC2 has been implicated in the pathogenesis of epilepsy. This study investigated the effects of this imbalance on GABAergic neurotransmission in certain brain regions. The results showed depolarized GABAergic signals in pyramidal neurons, and the specific NKCC1 inhibitor bumetanide effectively dampened these signals. Additionally, FCD patients exhibited altered expression and distribution of KCC2.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Chemistry, Multidisciplinary
Archie Brown, Nur Farah Meor Azlan, Zhijuan Wu, Jinwei Zhang
Summary: Hypertension is a common health issue globally, with Gordon's syndrome being a form of secondary hypertension that may result from mutations in key genes. Treatment for Gordon's syndrome mainly involves the use of thiazide diuretics, but they come with side effects, leading to research efforts focusing on developing novel inhibitory molecules.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Cell Biology
Anastasia Rigkou, Attila Magyar, Jan Manuel Speer, Eleni Roussa
Summary: The study demonstrates that TGF-beta 2 regulates KCC2 transcription in immature neurons, possibly acting upstream of AP2 beta.
Review
Neurosciences
Kelvin K. Hui, Thomas E. Chater, Yukiko Goda, Motomasa Tanaka
Summary: Excitatory-inhibitory (E-I) imbalance is a contributing factor to various neurodevelopmental disorders. Dysregulation of GABA neurotransmission and chloride homeostasis is associated with these abnormalities. Recent evidence suggests that the GABA-shift phenomenon may be involved in neuropsychiatric disorders. This review discusses the cell signaling and regulatory mechanisms underlying the GABA-shift, explores the interactions between GABAergic interneurons and other cell types, and outlines recent progress in targeting NKCC1 and KCC2 as a therapeutic strategy.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Nicholas L. Weilinger, Leigh E. Wicki-Stordeur, Christopher J. Groten, Jeffrey M. LeDue, Kristopher T. Kahle, Brian A. MacVicar
Summary: Intracellular chloride ion concentration plays a critical role in neuronal functions. The study reveals that NMDA-induced high chloride ion subdomains contribute to dendritic swelling in stroke-like conditions. This process relies on calcium influx and the activation of SK channels. These findings provide insights into the development of neurological disorders.
Article
Genetics & Heredity
Monis Bilal Shamsi, Mohamed Saleh, Makki Almuntashri, Essa Alharby, Manar Samman, Roy W. A. Peake, Fatima M. Al-Fadhli, Ali Alasmari, Eissa A. Faqeih, Naif A. M. Almontashiri
Summary: Heterozygous pathogenic variants in SLC12A2 have been linked to nonsyndromic hearing loss, while homozygous loss-of-function variants have been associated with syndromic intellectual disability. Variants in the c-terminal domain of the SLC12A2 gene seem to play a critical role in the functioning of the encoded co-transporter protein. The study provides additional confirmation of the autosomal recessive SLC12A2 disease.
JOURNAL OF HUMAN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Jiangning Yu, Guoxiang Wang, Zhiyun Chen, Li Wan, Jing Zhou, Jingyi Cai, Xu Liu, Yun Wang
Summary: In this study, the researchers discovered that PKHD1L1, encoded by Pkhd1l1, is widely distributed in neurons in the central nervous system (CNS) of mice. Disruption of PKHD1L1 leads to increased susceptibility to induced seizures in mice. The disturbance of PKHD1L1 activates the MAPK/ERK-Calpain pathway, resulting in the degradation of KCC2 and impaired expression and function of membrane KCC2. Reduction of membrane KCC2 is associated with impaired inhibitory ability of GABA receptors, ultimately leading to increased susceptibility to epileptic seizures. This study provides new insights into the role of PKHD1L1 in maintaining neuronal excitability and reveals a potential therapeutic target for PKD-related seizures.
HUMAN MOLECULAR GENETICS
(2023)
Article
Endocrinology & Metabolism
Yoshio Takei, Masaaki Ando, Marty K. S. Wong, Takehiro Tsukada
Summary: This study investigates the molecular mechanisms of transepithelial Cl- transport in the intestine of seawater-acclimated eels, and reveals that GN stimulates Cl- secretion. The DNDS-sensitive anion exchanger (AE) and Na+-HCO3- cotransporter (NBC) play a crucial role in Cl- uptake at the basolateral side, while an unknown DPC-sensitive Cl- channel (ClC) is responsible for Cl- secretion at the mucosal side.
GENERAL AND COMPARATIVE ENDOCRINOLOGY
(2022)
Article
Peripheral Vascular Disease
Aihua Wu, Martin J. Wolley, Qi Wu, Richard D. Gordon, Robert A. Fenton, Michael Stowasser
Summary: This study found significant changes in protein abundance in uEVs of PA patients undergoing fludrocortisone suppression testing, with a decrease in pendrin and an increase in ROMK. Co-administration of mineralocorticoid and KCl in PA patients may lead to these alterations.
JOURNAL OF HUMAN HYPERTENSION
(2021)
Article
Biochemistry & Molecular Biology
R. Ganugula, M. Deng, M. Arora, H. -L. Pan, M. N. V. Ravi Kumar
ACS CHEMICAL NEUROSCIENCE
(2019)
Article
Biochemistry & Molecular Biology
Youfang Chen, Shao-Rui Chen, Hong Chen, Jixiang Zhang, Hui-Lin Pan
JOURNAL OF NEUROCHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Meichun Deng, Shao-Rui Chen, Hong Chen, Yi Luo, Yingchun Dong, Hui-Lin Pan
JOURNAL OF NEUROCHEMISTRY
(2019)
Article
Neurosciences
Jie Sun, Shao-Rui Chen, Hong Chen, Hui-Lin Pan
JOURNAL OF PHYSIOLOGY-LONDON
(2019)
Article
Anesthesiology
Meichun Deng, Shao-Rui Chen, Hong Chen, Hui-Lin Pan
Article
Biochemistry & Molecular Biology
Yuying Huang, Shao-Rui Chen, Hong Chen, Hui-Lin Pan
JOURNAL OF NEUROCHEMISTRY
(2019)
Article
Immunology
Hong-Chun Xiang, Li-Xue Lin, Xue-Fei Hu, He Zhu, Hong-Ping Li, Ru-Yue Zhang, Liang Hu, Wen-Tao Liu, Yi-Lin Zhao, Yang Shu, Hui-Lin Pan, Man Li
JOURNAL OF NEUROINFLAMMATION
(2019)
Article
Cell Biology
Wenqiong Xu, Hongyi Zhou, Hongzhuan Xuan, Pradip Saha, Gongxian Wang, Weiqin Chen
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2019)
Article
Pharmacology & Pharmacy
Shao-Rui Chen, Jixiang Zhang, Hong Chen, Hui-Lin Pan
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2019)
Article
Endocrinology & Metabolism
Hongyi Zhou, Cheng Xu, Hakjoo Lee, Yisang Yoon, Weiqin Chen
MOLECULAR METABOLISM
(2020)
Article
Biochemistry & Molecular Biology
Jinhua Liu, Tong Wen, Kunzhe Dong, Xiangqin He, Hongyi Zhou, Jian Shen, Zurong Fu, Guoqing Hu, Wenxia Ma, Jie Li, Wenjuan Wang, Liang Wang, Brynn N. Akerberg, Jiqian Xu, Islam Osman, Zeqi Zheng, Wang Wang, Quansheng Du, William T. Pu, Meixiang Xiang, Weiqin Chen, Huabo Su, Wei Zhang, Jiliang Zhou
Summary: The Hippo signaling effector, TEAD1, is crucial for the survival of postmitotic cardiomyocytes, and its loss leads to dilated cardiomyopathy and activation of necroptosis. TEAD1 directly activates nuclear DNA-encoded mitochondrial genes necessary for ATP synthesis, highlighting its role in maintaining cardiomyocyte survival.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Hongyi Zhou, Huabo Su, Weiqin Chen
Summary: The study reveals that neddylation plays a crucial role in myoblast differentiation by regulating class IIa and III histone deacetylases. This provides new insights into the mechanisms of muscle disease and regeneration, highlighting the importance of neddylation in controlling the myogenic program.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Guichang Zou, Qi Chen, Kai Chen, Xin Zuo, Yushu Ge, Yiwen Hou, Tao Pan, Huilin Pan, Dan Liu, Li Zhang, Wei Xiong
Article
Medicine, Research & Experimental
Hongyi Zhou, Xinnuo Lei, Yun Yan, Todd Lydic, Jie Li, Neal L. Weintraub, Huabo Su, Weiqin Chen
Review
Biochemistry & Molecular Biology
Meichun Deng, Shao-Rui Chen, Hui-Lin Pan
CELLULAR AND MOLECULAR LIFE SCIENCES
(2019)