大鼠海马JNK信号通路活性改变:年龄、阿尔茨海默病样病理发展和JNK抑制剂IQ-1S的影响

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Natalia A. Muraleva, Anna A. Zhdankina, Andrey I. Khlebnikov, Nataliya G. Kolosova
{"title":"大鼠海马JNK信号通路活性改变:年龄、阿尔茨海默病样病理发展和JNK抑制剂IQ-1S的影响","authors":"Natalia A. Muraleva,&nbsp;Anna A. Zhdankina,&nbsp;Andrey I. Khlebnikov,&nbsp;Nataliya G. Kolosova","doi":"10.1134/S0006297924603903","DOIUrl":null,"url":null,"abstract":"<p>Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and the leading cause of senile dementia. The key risk factor for a more common (&gt;95% of cases) sporadic form of AD is age. So far, there are no effective methods for AD prevention or treatment. A growing body of evidence indicates that the development of AD and other neurodegenerative diseases is associated with the activation of mitogen-activated protein kinase (MAPK) pathways, and JNK signaling pathway is considered as a potential target for the prevention and treatment of AD. However, the information on alterations in its activity in ontogenesis, which are evaluated by changes in the phosphorylation of its components, is extremely limited. The aim of this study was to compare age-related changes in the activity of JNK signaling pathway in the hippocampus of Wistar rats and senescence-accelerated OXYS rats (which spontaneously develop the key symptoms of AD-like pathology) and to evaluate the effect of the selective JNK3 inhibitor IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt). The ability of IQ-1S to suppress accelerated brain aging in OXYS rat has been proven previously, but the effect of this inhibitor on the JNK activity has not been studied. Here, we showed that with age, the activity of the JNK signaling pathway increased in the hippocampus of rats of both strains. At the same time, the manifestation and active progression of AD-like pathology in OXYS rats was accompanied by the increase in the phosphorylation level of the key kinase of this signaling pathway, JNK3, and its target proteins compared to Wistar rats, which allowed us to suggest JNK3 as a potential target for interventions aimed at preventing neurodegenerative processes. This suggestion was supported by the fact that the neuroprotective effect of the selective JNK3 inhibitor IQ-1S and its ability to suppress the development of neurodegenerative processes in OXYS rats were associated with a decrease in the phosphorylation levels of JNK3, c-Jun, APP, and Tau in the hippocampus.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 2","pages":"265 - 275"},"PeriodicalIF":2.3000,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"JNK Signaling Pathway Activity Alterations in the Rat Hippocampus: Effect of Age, Alzheimer’s Disease-Like Pathology Development, and the JNK Inhibitor IQ-1S\",\"authors\":\"Natalia A. Muraleva,&nbsp;Anna A. Zhdankina,&nbsp;Andrey I. Khlebnikov,&nbsp;Nataliya G. Kolosova\",\"doi\":\"10.1134/S0006297924603903\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and the leading cause of senile dementia. The key risk factor for a more common (&gt;95% of cases) sporadic form of AD is age. So far, there are no effective methods for AD prevention or treatment. A growing body of evidence indicates that the development of AD and other neurodegenerative diseases is associated with the activation of mitogen-activated protein kinase (MAPK) pathways, and JNK signaling pathway is considered as a potential target for the prevention and treatment of AD. However, the information on alterations in its activity in ontogenesis, which are evaluated by changes in the phosphorylation of its components, is extremely limited. The aim of this study was to compare age-related changes in the activity of JNK signaling pathway in the hippocampus of Wistar rats and senescence-accelerated OXYS rats (which spontaneously develop the key symptoms of AD-like pathology) and to evaluate the effect of the selective JNK3 inhibitor IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt). The ability of IQ-1S to suppress accelerated brain aging in OXYS rat has been proven previously, but the effect of this inhibitor on the JNK activity has not been studied. Here, we showed that with age, the activity of the JNK signaling pathway increased in the hippocampus of rats of both strains. At the same time, the manifestation and active progression of AD-like pathology in OXYS rats was accompanied by the increase in the phosphorylation level of the key kinase of this signaling pathway, JNK3, and its target proteins compared to Wistar rats, which allowed us to suggest JNK3 as a potential target for interventions aimed at preventing neurodegenerative processes. This suggestion was supported by the fact that the neuroprotective effect of the selective JNK3 inhibitor IQ-1S and its ability to suppress the development of neurodegenerative processes in OXYS rats were associated with a decrease in the phosphorylation levels of JNK3, c-Jun, APP, and Tau in the hippocampus.</p>\",\"PeriodicalId\":483,\"journal\":{\"name\":\"Biochemistry (Moscow)\",\"volume\":\"90 2\",\"pages\":\"265 - 275\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-04-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemistry (Moscow)\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1134/S0006297924603903\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemistry (Moscow)","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1134/S0006297924603903","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

阿尔茨海默病(AD)是一种多因素神经退行性疾病,是老年痴呆症的主要原因。对于更常见(95%的病例)的散发性阿尔茨海默病来说,关键的危险因素是年龄。到目前为止,还没有有效的预防或治疗阿尔茨海默病的方法。越来越多的证据表明,AD等神经退行性疾病的发生与丝裂原活化蛋白激酶(MAPK)通路的激活有关,JNK信号通路被认为是预防和治疗AD的潜在靶点。然而,通过其组分磷酸化的变化来评估其在个体发生中的活性变化的信息是非常有限的。本研究的目的是比较Wistar大鼠和衰老加速的OXYS大鼠(自发出现ad样病理的关键症状)海马中JNK信号通路活性的年龄相关变化,并评估JNK3选择性抑制剂IQ-1S (11h -吲哚[1,2-b]喹诺沙林-11-肟钠盐)的作用。IQ-1S抑制OXYS大鼠大脑加速衰老的能力已被证实,但该抑制剂对JNK活性的影响尚未被研究。在这里,我们发现随着年龄的增长,两个品系的大鼠海马中JNK信号通路的活性增加。同时,与Wistar大鼠相比,OXYS大鼠ad样病理的表现和积极进展伴随着该信号通路关键激酶JNK3及其靶蛋白磷酸化水平的升高,这使我们建议JNK3作为预防神经退行性过程干预的潜在靶点。选择性JNK3抑制剂IQ-1S的神经保护作用及其抑制OXYS大鼠神经退行性过程的能力与海马中JNK3、c-Jun、APP和Tau磷酸化水平的降低有关,这一事实支持了这一观点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
JNK Signaling Pathway Activity Alterations in the Rat Hippocampus: Effect of Age, Alzheimer’s Disease-Like Pathology Development, and the JNK Inhibitor IQ-1S

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and the leading cause of senile dementia. The key risk factor for a more common (>95% of cases) sporadic form of AD is age. So far, there are no effective methods for AD prevention or treatment. A growing body of evidence indicates that the development of AD and other neurodegenerative diseases is associated with the activation of mitogen-activated protein kinase (MAPK) pathways, and JNK signaling pathway is considered as a potential target for the prevention and treatment of AD. However, the information on alterations in its activity in ontogenesis, which are evaluated by changes in the phosphorylation of its components, is extremely limited. The aim of this study was to compare age-related changes in the activity of JNK signaling pathway in the hippocampus of Wistar rats and senescence-accelerated OXYS rats (which spontaneously develop the key symptoms of AD-like pathology) and to evaluate the effect of the selective JNK3 inhibitor IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt). The ability of IQ-1S to suppress accelerated brain aging in OXYS rat has been proven previously, but the effect of this inhibitor on the JNK activity has not been studied. Here, we showed that with age, the activity of the JNK signaling pathway increased in the hippocampus of rats of both strains. At the same time, the manifestation and active progression of AD-like pathology in OXYS rats was accompanied by the increase in the phosphorylation level of the key kinase of this signaling pathway, JNK3, and its target proteins compared to Wistar rats, which allowed us to suggest JNK3 as a potential target for interventions aimed at preventing neurodegenerative processes. This suggestion was supported by the fact that the neuroprotective effect of the selective JNK3 inhibitor IQ-1S and its ability to suppress the development of neurodegenerative processes in OXYS rats were associated with a decrease in the phosphorylation levels of JNK3, c-Jun, APP, and Tau in the hippocampus.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Biochemistry (Moscow)
Biochemistry (Moscow) 生物-生化与分子生物学
CiteScore
4.70
自引率
3.60%
发文量
139
审稿时长
2 months
期刊介绍: Biochemistry (Moscow) is the journal that includes research papers in all fields of biochemistry as well as biochemical aspects of molecular biology, bioorganic chemistry, microbiology, immunology, physiology, and biomedical sciences. Coverage also extends to new experimental methods in biochemistry, theoretical contributions of biochemical importance, reviews of contemporary biochemical topics, and mini-reviews (News in Biochemistry).
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信