激酶的基因突变:对帕金森病已上市抑制剂和未开发靶点的全面回顾。

IF 2.7 4区 医学 Q2 CLINICAL NEUROLOGY
Neurological Sciences Pub Date : 2025-04-01 Epub Date: 2025-01-06 DOI:10.1007/s10072-024-07970-2
Amir Raza, Jeevika Raina, Sanjeev Kumar Sahu, Pankaj Wadhwa
{"title":"激酶的基因突变:对帕金森病已上市抑制剂和未开发靶点的全面回顾。","authors":"Amir Raza, Jeevika Raina, Sanjeev Kumar Sahu, Pankaj Wadhwa","doi":"10.1007/s10072-024-07970-2","DOIUrl":null,"url":null,"abstract":"<p><p>This comprehensive review navigates the landscape of genetic mutations in kinases, offering a thorough examination of both marketed inhibitors and unexplored targets in the context of Parkinson's Disease (PD). Although existing treatments for PD primarily center on symptom management, progress in comprehending the molecular foundations of the disease has opened avenues for targeted therapeutic approaches. This review encompasses an in-depth analysis of four key kinases-PINK1, LRRK2, GAK, and PRKRA-revealing that LRRK2 has garnered the most attention with a plethora of marketed inhibitors. However, the study underscores notable gaps in the exploration of inhibitors for PINK1, GAK, and a complete absence for PRKRA. The observed scarcity of inhibitors for these kinases emphasizes a significant area of untapped potential in PD therapeutics. By drawing attention to these unexplored targets, the review highlights the urgent need for focused research and drug development efforts to diversify the therapeutic landscape, potentially providing novel interventions for halting or slowing the progression of PD.</p>","PeriodicalId":19191,"journal":{"name":"Neurological Sciences","volume":" ","pages":"1509-1524"},"PeriodicalIF":2.7000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic mutations in kinases: a comprehensive review on marketed inhibitors and unexplored targets in Parkinson's disease.\",\"authors\":\"Amir Raza, Jeevika Raina, Sanjeev Kumar Sahu, Pankaj Wadhwa\",\"doi\":\"10.1007/s10072-024-07970-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This comprehensive review navigates the landscape of genetic mutations in kinases, offering a thorough examination of both marketed inhibitors and unexplored targets in the context of Parkinson's Disease (PD). Although existing treatments for PD primarily center on symptom management, progress in comprehending the molecular foundations of the disease has opened avenues for targeted therapeutic approaches. This review encompasses an in-depth analysis of four key kinases-PINK1, LRRK2, GAK, and PRKRA-revealing that LRRK2 has garnered the most attention with a plethora of marketed inhibitors. However, the study underscores notable gaps in the exploration of inhibitors for PINK1, GAK, and a complete absence for PRKRA. The observed scarcity of inhibitors for these kinases emphasizes a significant area of untapped potential in PD therapeutics. By drawing attention to these unexplored targets, the review highlights the urgent need for focused research and drug development efforts to diversify the therapeutic landscape, potentially providing novel interventions for halting or slowing the progression of PD.</p>\",\"PeriodicalId\":19191,\"journal\":{\"name\":\"Neurological Sciences\",\"volume\":\" \",\"pages\":\"1509-1524\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurological Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10072-024-07970-2\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurological Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10072-024-07970-2","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

这篇全面的综述导航了激酶基因突变的景观,在帕金森病(PD)的背景下,对已上市的抑制剂和未开发的靶点进行了彻底的检查。尽管现有的PD治疗主要集中在症状管理上,但在了解疾病分子基础方面的进展为靶向治疗方法开辟了道路。这篇综述包含了四个关键激酶——pink1、LRRK2、GAK和prkra的深入分析,揭示了LRRK2已经获得了大量市场抑制剂的关注。然而,该研究强调了PINK1、GAK抑制剂探索方面的显著空白,以及PRKRA抑制剂的完全缺失。观察到的这些激酶抑制剂的稀缺性强调了PD治疗中尚未开发潜力的重要领域。通过关注这些未开发的靶点,该综述强调了迫切需要集中研究和药物开发工作,以使治疗前景多样化,可能为阻止或减缓PD的进展提供新的干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genetic mutations in kinases: a comprehensive review on marketed inhibitors and unexplored targets in Parkinson's disease.

This comprehensive review navigates the landscape of genetic mutations in kinases, offering a thorough examination of both marketed inhibitors and unexplored targets in the context of Parkinson's Disease (PD). Although existing treatments for PD primarily center on symptom management, progress in comprehending the molecular foundations of the disease has opened avenues for targeted therapeutic approaches. This review encompasses an in-depth analysis of four key kinases-PINK1, LRRK2, GAK, and PRKRA-revealing that LRRK2 has garnered the most attention with a plethora of marketed inhibitors. However, the study underscores notable gaps in the exploration of inhibitors for PINK1, GAK, and a complete absence for PRKRA. The observed scarcity of inhibitors for these kinases emphasizes a significant area of untapped potential in PD therapeutics. By drawing attention to these unexplored targets, the review highlights the urgent need for focused research and drug development efforts to diversify the therapeutic landscape, potentially providing novel interventions for halting or slowing the progression of PD.

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
Neurological Sciences
Neurological Sciences 医学-临床神经学
CiteScore
6.10
自引率
3.00%
发文量
743
审稿时长
4 months
期刊介绍: Neurological Sciences is intended to provide a medium for the communication of results and ideas in the field of neuroscience. The journal welcomes contributions in both the basic and clinical aspects of the neurosciences. The official language of the journal is English. Reports are published in the form of original articles, short communications, editorials, reviews and letters to the editor. Original articles present the results of experimental or clinical studies in the neurosciences, while short communications are succinct reports permitting the rapid publication of novel results. Original contributions may be submitted for the special sections History of Neurology, Health Care and Neurological Digressions - a forum for cultural topics related to the neurosciences. The journal also publishes correspondence book reviews, meeting reports and announcements.
×
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