Article
Multidisciplinary Sciences
Jonathan Madar, Namrata Tiwari, Cristina Smith, Divya Sharma, Shanwei Shen, Alsiddig Elmahdi, Liya Y. Qiao
Summary: Piezo2 in mucosa and primary afferents mediates colonic mechanical sensation. Activation of Piezo2 regulates colonic mechanical sensitivity in a sex-dependent manner. Clozapine N-oxide induced activation of Piezo2 causes colonic hypersensitivity in male mice and dyspnea in female mice.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Ludivine Pidoux, Kevin Delanoe, Julie Barbier, Fabien Marchand, Eric Lingueglia, Emmanuel Deval
Summary: LPC, a member of the phospholipid family, plays an important role in pain modulation by regulating various pain-related ion channels, such as ASIC3, which is significant for understanding chronic pain conditions.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Sven Kuspiel, Dominik Wiemuth, Stefan Gruender
Summary: Research shows that the neuropeptide nocistatin does not directly activate ASIC1a channels, but rather indirectly activates them by acidifying the bath solution. This indicates the complexity of the regulatory mechanism of acid-sensing ion channels.
Article
Multidisciplinary Sciences
Ben Cristofori-Armstrong, Elena Budusan, Lachlan D. Rash
Summary: The study compared the potency and mechanism of action of mambalgins on rat and human ASIC1 variants, revealing that mambalgin-3 weakly inhibits human ASIC1b under severe acidosis, but potentiates currents under mild/moderate acidosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Xu Han, Yawen Zhang, Allen Lee, Zhaoshen Li, Jun Gao, Xiaoyin Wu, Jiulong Zhao, Hui Wang, Di Chen, Duowu Zou, Chung Owyang
Summary: This study found that the expression of ASIC1 and 3 is increased in GERD patients and rodent models of reflux esophagitis and non-erosive reflux disease. In addition, it was observed that DRG neurons from RE animals showed hyperexcitability. However, the injection of ASIC specific inhibitors and silencing of ASIC1 and 3 genes prevented visceral hypersensitivity. These results suggest that upregulation of ASIC1 and 3 may contribute to visceral hypersensitivity in GERD.
Article
Neurosciences
Miguel Salinas, Pascal Kessler, Dominique Douguet, Daad Sarraf, Nicolo Tonali, Robert Thai, Denis Servent, Eric Lingueglia
Summary: This study elucidated the inhibition mechanism of the snake venom toxin Mamb-1 on the acid-sensing ion channel ASIC1a through structure-activity relationship, molecular dynamics simulation, and experimental research. It provides important insights for further improvement and optimization of ASIC blockers.
Review
Neurosciences
Victoria S. Foster, Lachlan D. Rash, Glenn F. King, Michelle M. Rank
Summary: This review discusses the expression of ASICs in peripheral and CNS-resident immune cells, and how their activation during pathological tissue acidosis can affect immune cell function, modulating inflammatory pathology in the CNS. It also highlights the importance of understanding the contribution of ASICs to immune cell function in neuropathology for potential therapeutic benefits.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Critical Care Medicine
Victoria S. Foster, Natalie J. Saez, Ellen R. Gillespie, Trisha Jogia, Chantelle Reid, Snezana Maljevic, Woncheol Jung, Hong W. Lao, Marc J. Ruitenberg, Glenn F. King
Summary: Acid-sensing ion channel 1a (ASIC1a) is widely expressed in the central nervous system and immune cells. Its role in spinal cord injury (SCI) is controversial, with studies reporting both improvement and exacerbation of pathology. In this study, genetic ablation of ASIC1a in mice resulted in worsened locomotor ability and increased lesion size, while pharmacological inhibition with Hi1a led to accelerated neuronal cell loss at the lesion site without affecting locomotor recovery or immune cell responses.
JOURNAL OF NEUROTRAUMA
(2023)
Article
Neurosciences
Eric Brown, Ayma F. Malik, Elizabeth R. Moese, Abigail F. McElroy, Angelo C. Lepore
Summary: Neuropathic pain (NP) is a common and debilitating comorbidity of spinal cord injury (SCI). This study investigates the neural activity changes in the pain circuitry following cervical spinal cord injury. The findings reveal complex changes in neuronal activation, with increased activation in some neurons and decreased activation in inhibitory neurons.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biology
Yi Liu, Jichun Ma, Renee L. DesJarlais, Rebecca Hagan, Jason Rech, David Lin, Changlu Liu, Robyn Miller, Jeffrey Schoellerman, Jinquan Luo, Michael Letavic, Bruce Grasberger, Michael Maher
Summary: Liu et al's study reveals that small molecules can allosterically inhibit ASIC1 channel activation and desensitization by binding at the acidic pocket and stabilizing the closed state of the channel.
COMMUNICATIONS BIOLOGY
(2021)
Article
Neurosciences
Hong-Jun Wang, Fu-Chao Zhang, Timothy W. Xu, Yu-Cheng Xu, Yuan-Qing Tian, Yan-Yan Wu, Ji-Tian Xu, Shufen Hu, Guang-Yin Xu
Summary: The aim of this study was to investigate the mechanism of how DNMT1 mediates the analgesic effect of folic acid (FA) on gastric hypersensitivity (GHS) induced by prenatal maternal stress (PMS). The expression of DNMT1, DNMT3a, DNMT3b, and ASIC1 were detected and the effect of FA and DNMT1 on GHS and neuronal excitability were explored.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Neurosciences
Yan Fu, Liting Sun, Fengting Zhu, Wei Xia, Ting Wen, Ruilong Xia, Xin Yu, Dan Xu, Changgeng Peng
Summary: Neuropathic pain caused by spinal cord injury is a long-term disturbance for patients, and the underlying mechanisms are still unclear. This study found that the abnormal expression of Nav1.7 in SDH is associated with NP. Pharmacological studies demonstrated that the blood-brain-barrier permeable Nav1.7 inhibitor GNE-0439 has a significant analgesic effect on NP in SCI mice.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Endocrinology & Metabolism
Wei Wang, Mengyun Xu, Jiayin Yue, Qilun Zhang, Xiaomin Nie, Yan Jin, Zhi Zhang
Summary: ASIC1a in the PVN may serve as a potential new target for the therapeutic intervention of metabolic disorders.
Article
Cell Biology
Kangcheng Zhao, Ran An, Qian Xiang, Gaocai Li, Kun Wang, Yu Song, Zhiwei Liao, Shuai Li, Wenbin Hua, Xiaobo Feng, Xinghuo Wu, Yukun Zhang, Abhirup Das, Cao Yang
Summary: Extracellular lactate regulates intercellular reactive oxygen species (ROS) levels through ASIC1 and ASIC3, activating the NF-kappa B signaling pathway to promote NLRP3 inflammasome activation and IL-1 beta release, ultimately contributing to NP degeneration.
CELL PROLIFERATION
(2021)
Article
Cell Biology
Shangrila Parvin, Clintoria R. Williams, Simone A. Jarrett, Sandra M. Garraway
Summary: This study revealed that spinal cord injury leads to robust systemic inflammation extending to the kidney, impacting renal pathophysiology and function. Elevated levels of inflammatory cytokines were observed in both the spinal cord and kidney post-SCI, emphasizing the importance of renal inflammation in SCI outcomes.