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激酶中的基因突变:帕金森病上市抑制剂及未探索靶点的综合综述

Genetic mutations in kinases: a comprehensive review on marketed inhibitors and unexplored targets in Parkinson's disease.

作者信息

Raza Amir, Raina Jeevika, Sahu Sanjeev Kumar, Wadhwa Pankaj

机构信息

School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar- Grand Trunk Rd, Phagwara, Punjab, India.

出版信息

Neurol Sci. 2025 Apr;46(4):1509-1524. doi: 10.1007/s10072-024-07970-2. Epub 2025 Jan 6.

Abstract

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.

摘要

这篇全面的综述探讨了激酶基因突变的情况,在帕金森病(PD)的背景下,对已上市的抑制剂和未探索的靶点进行了全面研究。尽管目前针对PD的治疗主要集中在症状管理上,但在理解该疾病分子基础方面取得的进展为靶向治疗方法开辟了道路。这篇综述深入分析了四种关键激酶——PINK1、LRRK2、GAK和PRKRA,发现LRRK2因有大量已上市的抑制剂而备受关注。然而,该研究强调在PINK1、GAK抑制剂的探索方面存在显著差距,而PRKRA则完全没有相关研究。这些激酶抑制剂的稀缺表明在PD治疗领域存在巨大的未开发潜力。通过关注这些未探索的靶点,该综述强调了迫切需要集中研究和药物开发工作,以实现治疗方法的多样化,有可能为阻止或减缓PD的进展提供新的干预措施。

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