Review
Neurosciences
Jose Afonso Correa da Silva, Nadja Schroeder
Summary: It is believed that neurological diseases caused by degenerative conditions may have abnormal influx of Ca2+ through glutamate receptors. In addition to the NMDAR, AMPARs can also mediate neurotoxic Ca2+ influx, especially when the GluA2 subunit is absent or disrupted. The increase of Ca2+-permeable AMPA receptors (CP-AMPARs) is associated with behavioral changes and various neurodegenerative, neuroinflammatory, and neurotoxic conditions, suggesting a potential role in the emergence and evolution of central nervous system (CNS) pathological conditions. This article summarizes and discusses studies on changes in the composition of AMPARs and their effects, aiming to understand the therapeutic potential of CP-AMPAR in neurological diseases.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2023)
Article
Biology
Anastasiya Zaytseva, Evelina Bouckova, McKennon J. Wiles, Madison H. Wustrau, Isabella G. Schmidt, Hadassah Mendez-Vazquez, Latika Khatri, Seonil Kim
Summary: Ketamine enhances neuronal activity and synaptic strength by reducing calcineurin activity, leading to rapid antidepressant effects.
Review
Neurosciences
Stuart G. Cull-Candy, Mark Farrant
Summary: CP-AMPARs are important regulators of synaptic plasticity, with their functional characteristics being modulated by auxiliary subunits and involved in various forms of central synaptic plasticity. Maladaptive synaptic plasticity and neurological disorders often involve changes in CP-AMPAR expression, such as those induced by inflammatory pain, fear conditioning, and cocaine exposure.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Multidisciplinary Sciences
Beatriz Herguedas, Bianka K. Kohegyi, Jan-Niklas Dohrke, Jake F. Watson, Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, Ingo H. Greger
Summary: This study reveals how the auxiliary subunit TARP-gamma 8 modulates the gating kinetics, ion conductance, and rectification properties of AMPA receptors, providing important insights into the functional mechanism of AMPA glutamate receptors.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Shuo Li, Sumana Raychaudhuri, Stephen Alexander Lee, Marisa M. Brockmann, Jing Wang, Grant Kusick, Christine Prater, Sarah Syed, Hanieh Falahati, Raul Ramos, Tomas M. Bartol, Eric Hosy, Shigeki Watanabe
Summary: Neurotransmitter release in synapses is influenced by action potentials, with synchronous and asynchronous release sites segregated within active zones, aligned with AMPA and NMDA receptor clusters respectively. This organization leads to efficient activation of NMDA receptors, enhancing membrane depolarization through AMPA receptors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Denis P. Laryushkin, Sergei A. Maiorov, Valery P. Zinchenko, Valentina N. Mal'tseva, Sergei G. Gaidin, Artem M. Kosenkov
Summary: This study investigates the role of ionotropic glutamate receptors (iGluRs) in the generation of paroxysmal depolarization shift (PDS) and the dependence of PDS pattern on neuronal membrane potential. The results show that external stimuli play a crucial role in PDS induction. AMPA receptors are necessary for PDS generation, while NMDA and kainate receptors modulate paroxysmal activity. Agonists of G(i)-coupled receptors suppress PDS generation, suggesting a potential approach for epilepsy pharmacotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Hong-Yu Liang, Huan-Xin Yin, Shu-Fang Li, Yong Chen, Ying-Jie Zhao, Wei Hu, Ren-Peng Zhou
Summary: This article introduces the major calcium-permeable channels involved in the pathogenesis of rheumatoid arthritis (RA) and explains the specific roles and mechanisms of these calcium-permeable channels in the pathogenesis of RA. It provides more comprehensive ideas and targets for the treatment of RA.
Review
Neurosciences
Changyong Guo, Yao-Ying Ma
Summary: Excitotoxicity is a key mechanism of cell loss in various diseases of the central and peripheral nervous systems. In addition to the previously established pathways, CP-AMPAR-mediated excitotoxicity is identified in multiple disease models. Specific manipulation of CP-AMPARs may be a more effective strategy to delay pathological changes with fewer side effects compared to blocking NMDARs.
FRONTIERS IN NEURAL CIRCUITS
(2021)
Article
Multidisciplinary Sciences
Fengfeng Niu, Yong Liu, Kang Sun, Shun Xu, Jiayuan Dong, Cong Yu, Kaige Yan, Zhiyi Wei
Summary: The study provides insights into the structural and functional regulation of myosin Va, revealing the molecular mechanisms of autoinhibition and activation as well as the specific activation mechanism dependent on multiple cargo adaptors.
Article
Biochemistry & Molecular Biology
Rostislav A. Sokolov, Irina V. Mukhina
Summary: Calcium is a crucial intracellular messenger in the brain that regulates various cell processes. In this study, the researchers used a fluorescent probe to investigate spontaneous Ca2+ events (SCEs) in neurons during culture maturation. They found that SCEs exhibited three different amplitude distributions and were dependent on extracellular Ca2+, neuronal network activity, and specific receptors and channels.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Review
Biochemistry & Molecular Biology
Tomasz Boczek, Ludmila Zylinska
Summary: The activity of specific populations of neurons in different brain areas plays a critical role in decision-making processes related to synaptic transmission, adaptations to external signals, and the maintenance of neural function. The endocannabinoid system (ECS) is identified as a vital control system in the central nervous system (CNS), allowing for rapid responses to synaptic processes and inducing long-term changes. Endocannabinoids are bioactive lipid mediators that act primarily through two receptors, CB1R and CB2R, which can regulate downstream Ca2+ signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Ian D. Coombs, Stuart G. Cull-Candy
Summary: The functional properties of AMPA receptors are crucial in shaping excitatory synaptic signaling in the brain. Understanding the behavior and regulation of single AMPAR channels is essential in unraveling how central synapses carry, process, and store information. Auxiliary subunits play a key role in regulating AMPAR channel properties and adding diversity, while single-channel studies reveal the unique behavior of AMPAR channels.
Article
Pharmacology & Pharmacy
Jimin Yu, Eunbi Cho, Huiyoung Kwon, Jieun Jeon, Jae Seong Sin, Jun Kwon Park, Ji-Su Kim, Ji Woong Choi, Se Jin Park, Mira Jun, Young Choon Lee, Jong Hoon Ryu, Jeongwon Lee, Minho Moon, Seungheon Lee, Jong Hyun Cho, Dong Hyun Kim
Summary: The lignan pinoresinol, found in Forsythia suspensa, has shown promising results in reducing memory deficits and synaptic dysfunction in an amyloid beta-induced AD-like mouse model. Pinoresinol enhances hippocampal long-term potentiation through Akt activation, ameliorating AD-like pathology and memory deficits without sensory dysfunction. These findings suggest that pinoresinol may be a potential candidate for Alzheimer's disease therapy by modulating synaptic functions.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biology
Valery Petrovich Zinchenko, Artem Mikhailovich Kosenkov, Sergei Gennadevich Gaidin, Alexander Igorevich Sergeev, Ludmila Petrovna Dolgacheva, Sultan Tuleukhanovich Tuleukhanov
Summary: In mature hippocampal neuroglial cultures, GABAergic neurons expressing CP-AMPARs and CP-KARs were identified, showing rapid sustained increase in calcium ions in response to agonists like domoic acid and ATPA. Additionally, the study revealed that the CP-AMPARs antagonist NASPM can enhance the calcium response in GABAergic neurons expressing CP-KARs, indicating a functional connection between neurons expressing CP-AMPARs and GABAergic neurons expressing CP-KARs. The results suggest that CP-KARs in inhibitory neurons may be involved in regulating GABA release during hyperexcitation.
Article
Pharmacology & Pharmacy
Jee Hyun Yi, Somin Moon, Eunbi Cho, Huiyoung Kwon, Seungjin Lee, Jieun Jeon, A. Young Park, Ye Hee Lee, Kyoung Ja Kwon, Jong Hoon Ryu, Se Jin Jeon, Chan Young Shin, Sang Hee Shim, Dong Hyun Kim
Summary: Alzheimer's disease is a common degenerative disease associated with dementia. This study found that hyperoside can enhance synaptic function and memory, and improve memory impairments by modulating the effect of CP-AMPARs on LTP.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Andrei M. Gigolaev, Alexey Kuzmenkov, Steve Peigneur, Valentin M. Tabakmakher, Ernesto L. Pinheiro-Junior, Anton O. Chugunov, Roman G. Efremov, Jan Tytgat, Alexander A. Vassilevski
FRONTIERS IN PHARMACOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Marianne van Cann, Alexey Kuzmenkov, Jorg Isensee, Alexander Andreev-Andrievskiy, Steve Peigneur, Georgii Khusainov, Antonina Berkut, Jan Tytgat, Alexander Vassilevski, Tim Hucho
Summary: The study identified a scorpion toxin, MeuNaTx alpha-1, from Mesobuthus eupeus venom, which modulates pain sensitization signaling in rat primary sensory neurons. The toxin showed dose-dependent effects on sensory neurons and its mechanism of action involves the Na(V)1.2 sodium channel.
Article
Biochemistry & Molecular Biology
Konstantin S. Mineev, Alexey Kuzmenkov, Alexander S. Arseniev, Alexander A. Vassilevski
Summary: Old world scorpions produce a variety of toxins called alpha-NaTx, which affect voltage-gated sodium channels. The selectivity of these toxins to mammals or insects is determined by a part called the specificity module. The spatial structure of a major toxin MeuNaTx alpha-1 from the venom of Mesobuthus eupeus shows a unique specificity module and structural diversity influenced by protein motifs such as the nest and niche.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Biophysics
Valentin M. Tabakmakher, Andrei M. Gigolaev, Steve Peigneur, Nikolay A. Krylov, Jan Tytgat, Anton O. Chugunov, Alexander A. Vassilevski, Roman G. Efremov
Summary: In this study, a combined molecular modeling approach was utilized to design a series of Tk-hefu-2 derivatives with improved affinity to K(V)1.3 while maintaining specificity. The most active mutant Tk-hefu-10 showed significantly higher inhibitory activity, demonstrating the potential of alpha-hairpinins as a scaffold for rational design of ion channel inhibitors. This work represents a promising strategy for increasing the success rate in molecular design of ion channel inhibitors.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
V. M. Tabakmakher, A. Kuzmenkov, A. M. Gigolaev, E. L. Pinheiro, S. Peigneur, R. G. Efremov, J. Tytgat, A. A. Vassilevski
Summary: The study reports the isolation of a peptide toxin MeKTx13-3 from scorpion venom and its artificial derivative MeKTx13-3_RMRH, which shows increased selectivity towards K(V)1.1. Through computer simulations, researchers demonstrate that the preference of the new ligand for K(V)1.1 can be achieved through specific positioning of the toxin in complex with the channel.
JOURNAL OF EVOLUTIONARY BIOCHEMISTRY AND PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
M. Yu. Myshkin, A. S. Paramonov, D. S. Kulbatskii, E. A. Surkova, A. A. Berkut, A. A. Vassilevski, E. N. Lyukmanova, M. P. Kirpichnikov, Z. O. Shenkarev
Summary: Voltage-gated sodium channels have modular architecture with five membrane domains, where peripheral voltage-sensing domains are responsible for channel activation and rapid inactivation. Gating modifier toxins from arthropod venoms interact with these domains, potentially serving as prototypes for new drugs. In this study, the toxin Hm-3 showed high affinity to VSD-III of human skeletal muscle Na(V)1.4 channel, with specific residues likely interacting with the channel and the lipid bilayer.
Article
Biochemistry & Molecular Biology
M. A. Chernykh, N. A. Kuldyushev, S. Peigneur, A. A. Berkut, J. Tytgat, R. G. Efremov, A. A. Vassilevski, A. O. Chugunov
Summary: The study showed that the double mutant derivative BeM9(EG) lost its activity on mammalian channels and became an insect toxin. Molecular dynamics simulations suggested that residues K8 and Y17 play an important role in stabilizing a specific conformation of BeM9 loops, and it is hypothesized that the replacement of these residues allosterically affects the efficiency of toxin binding to channels.
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Igor E. Kasheverov, Alexey I. Kuzmenkov, Denis S. Kudryavtsev, Ivan S. Chudetskiy, Irina V. Shelukhina, Evgeny P. Barykin, Igor A. Ivanov, Andrei E. Siniavin, Rustam H. Ziganshin, Mikhail S. Baranov, Victor I. Tsetlin, Alexander A. Vassilevski, Yuri N. Utkin
Summary: The study found that the introduction of a synthetic GFP chromophore induced a considerably lower decrease in affinity between protein and peptide neurotoxins and receptors compared to full-length GFP attachment. This new method can be used for visualizing nAChR in tissue slices and cell cultures.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Pharmacology & Pharmacy
Alexey I. Kuzmenkov, Steve Peigneur, Joshua A. Nasburg, Konstantin S. Mineev, Maxim V. Nikolaev, Ernesto Lopes Pinheiro-Junior, Alexander S. Arseniev, Heike Wulff, Jan Tytgat, Alexander A. Vassilevski
Summary: Apamin is a selective inhibitor of K(Ca)2 channels with no significant effects on other molecular targets. The spatial structure of apamin and its potential use as a pharmacological tool and drug design template for K(Ca)2 channels are supported by this study.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
A. M. Gigolaev, E. L. Pinheiro-Junior, S. Peigneur, J. Tytgat, A. A. Vassilevski
Summary: In this study, a highly potent and selective ligand for the potassium channel K(V)1.2 was obtained by modifying a scorpion peptide toxin. The modified peptide showed increased affinity and activity against K(V)1.2, while having lower affinity for other isoforms.
JOURNAL OF EVOLUTIONARY BIOCHEMISTRY AND PHYSIOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
A. Kuzmenkov, I. Chudetskiy, D. Prudnikova, A. Vassilevski
Meeting Abstract
Pharmacology & Pharmacy
M. van Cann, A. Kuzmenkov, J. Isensee, A. Andreev-Andrievskiy, S. Peigneur, G. Khusainov, A. Berkut, J. Tytgat, A. Vassilevski, T. Hucho
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Immunology
Sofie Fons, Line Ledsgaard, Maxim V. Nikolaev, Alexander A. Vassilevski, Christoffer V. Sorensen, Manon K. Chevalier, Michael Fiebig, Andreas H. Laustsen
FRONTIERS IN IMMUNOLOGY
(2020)
Meeting Abstract
Pharmacology & Pharmacy
Igor E. Kasheverov, Peter B. Oparin, Alexander A. Vassilevski, Igor A. Ivanov, Victor I. Tsetlin, Yuri N. Utkin
Meeting Abstract
Pharmacology & Pharmacy
Alexander Vassilevski
