更新于：2024-11-01

ASIC2

更新于：2024-11-01

基本信息

别名

ACCN、ACCN1、acid sensing ion channel subunit 2

+ [14]

简介

Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Heteromeric channel assembly seems to modulate.

关联

项与 ASIC2 相关的药物

TH-901

靶点

ASIC2

作用机制

ASIC2 inhibitors

在研机构-

原研机构

Theralpha S.A.S.

在研适应症-

非在研适应症

疼痛

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

NPI-507

靶点

ASIC2

作用机制

ASIC2 inhibitors

在研机构-

原研机构

Neuroprotect, Inc.

在研适应症-

非在研适应症

癫痫

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 ASIC2 相关的临床结果

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100 项与 ASIC2 相关的转化医学

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0 项与 ASIC2 相关的专利（医药）

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615

项与 ASIC2 相关的文献（医药）

2024-10-25·Science Advances

Mice lacking acid-sensing ion channel 2 in the medial prefrontal cortex exhibit social dominance

Article

作者: Naghavi, Farzaneh ; Lu, Hui ; Ge, Qian ; Ryan V, William G. ; Singh, Kritika ; Du, Jianyang ; Lin, Boren ; Park, Gyeongah ; Khan, Saira ; McCullumsmith, Robert E. ; Jin, Zhen ; Miller, Olivia Ann ; Imami, Ali Sajid

Social dominance is essential for maintaining a stable society and has both positive and negative impacts on social animals, including humans. However, the regulatory mechanisms governing social dominance, as well as the crucial regulators and biomarkers involved, remain poorly understood. We discover that mice lacking acid-sensing ion channel 2 (ASIC2) exhibit persistently higher social dominance than their wild-type cagemates. Conversely, overexpression of ASIC2 in the medial prefrontal cortex reverses the dominance hierarchy observed in ASIC2 knockout ( Asic2−/− ) mice. Asic2−/− neurons exhibit increased synaptic transmission and plasticity, potentially mediated by protein kinase A signaling pathway. Furthermore, ASIC2 plays distinct functional roles in excitatory and inhibitory neurons, thereby modulating the balance of neuronal activities underlying social dominance behaviors—a phenomenon suggestive of a cell subtype–specific mechanism. This research lays the groundwork for understanding the mechanisms of social dominance, offering potential insights for managing social disorders, such as depression and anxiety.

2024-09-01·The Journal of Pain

Genetic Risk Factors for Bortezomib-induced Neuropathic Pain in an Asian Population: A Genome-wide Association Study in South Korea

Article

作者: Byun, Ja Min ; Sung, Jung-Joon ; Yoon, Sung-Soo ; Lim, Ehyun ; Lee, Sung-Yeoun ; Kim, Dong-Ho ; Oh, Seog Bae ; Hong, Junshik ; Koh, Youngil ; Min, Young Gi ; Kim, Inho ; Shin, Dong-Yeop ; Park, Mi-Young

Bortezomib-induced neuropathic pain (BINP) poses a challenge in multiple myeloma (MM) treatment. Genetic factors play a key role in BINP susceptibility, but research has predominantly focused on Caucasian populations. This research explored novel genetic risk loci and pathways associated with BINP development in Korean MM patients while evaluating the reproducibility of variants from Caucasians. Clinical data and buffy coat samples from 185 MM patients on bortezomib were collected. The cohort was split into discovery and validation cohorts through random stratification of clinical risk factors for BINP. Genome-wide association study was performed on the discovery cohort (n = 74) with Infinium Global Screening Array-24 v3.0 BeadChip (654,027 single nucleotide polymorphism [SNPs]). Relevant biological pathways were identified using the pathway scoring algorithm. The top 20 SNPs were validated in the validation cohort (n = 111). Previously reported SNPs were validated in the entire cohort (n = 185). Pathway analysis of the genome-wide association study results identified 31 relevant pathways, including immune systems and endosomal vacuolar pathways. Among the top 20 SNPs from the discovery cohort, 16 were replicated, which included intronic variants in ASIC2 and SMOC2, recently implicated in nociception, as well as intergenic variants or long noncoding RNAs. None of the 17 previously reported SNPs remained significant in our cohort (rs2274578, P = .085). This study represents the first investigation of novel genetic loci and biological pathways associated with BINP occurrence. Our findings, in conjunction with existing Caucasian studies, expand the understanding of personalized risk prediction and disease mechanisms. PERSPECTIVE: This article is the first to explore novel genetic loci and pathways linked to BINP in Korean MM patients, offering novel insights beyond the existing research focused on Caucasian populations into personalized risk assessment and therapeutic strategies of BINP.

2024-08-01·Hypertension Research

Immunological insights into hypertension: unraveling triggers and potential therapeutic avenues

Review

作者: Paradis, Pierre ; Shokoples, Brandon G ; Schiffrin, Ernesto L

Hypertension remains the leading cause of morbidity and mortality worldwide. Despite its prevalence, the development of novel antihypertensive therapies has only recently accelerated, with novel agents not yet commercialized, leaving a substantial proportion of individuals resistant to existing treatments. The intricate pathophysiology of hypertension is now understood to involve chronic low-grade inflammation, which places the immune system in the spotlight as a potential target for new therapeutics. This review explores the factors that initiate and sustain an immune response in hypertension, offering insights into potential targets for new treatments. Several factors contribute to immune activation in hypertension, including diet and damage-associated molecular pattern (DAMP) generation. Diets rich in fat or sodium can promote inflammation by inducing intestinal barrier dysfunction and triggering salt-sensitive receptors in T cells and dendritic cells. DAMPs, such as extracellular adenosine triphosphate and heat-shock protein 70, are released during episodes of increased blood pressure, contributing to immune cell activation and inflammation. Unconventional innate-like γδ T cells contribute to initiating and maintaining an immune response through their potential involvement in antigen presentation and regulating cytokine-mediated responses. Immunologic memory, sustained through the formation of effector memory T cells after exposure to hypertensive insults, likely contributes to maintaining an immune response in hypertension. When exposed to hypertensive insults, these memory cells are rapidly activated and contribute to elevated blood pressure and end-organ damage. Evidence from human hypertension, although limited, supports the relevance of distinct immune pathways in hypertension, and highlights the potential of targeted immune interventions in human hypertension. Diet and acute bouts of high blood pressure result in the release of dietary triggers, neoantigens, and damage-associated molecular patterns (DAMPs), which promote immune system activation. Elements such as lipopolysaccharides (LPS), sodium, heat-shock protein (HSP)70, extracellular adenosine triphosphate (eATP), and growth arrest-specific 6 (GAS6) promote activation of innate immune cells such as dendritic cells (DCs) and monocytes (Mo) through their respective receptors (toll-like receptor [TLR]4, amiloride-sensitive epithelial sodium channel [ENaC], TLR2/4, P2X7 receptor [P2RX7], and Axl) leading to costimulatory molecule expression and interleukin (IL)-1β and IL-23 production. The neoantigens HSP70 and isolevuglandins (IsoLGs) are presented to T cells by DCs and possibly γδ T cells, triggering T cell activation, IL-17 and interferon (IFN)-γ production, and the formation of T effector memory (T_EM) cells in the kidney, perivascular adipose tissue, bone marrow, and spleen. Exposure of T_EM cells to their cognate antigen or previous activating stimuli causes these cells rapid expansion and activation. Cumulatively, this inflammatory state contributes to hypertension and end-organ damage. The figure was created using images from smart.servier.com and is licensed under a Creative Commons Attribution 4.0 license (CC BY 4.0).