Glutamate Receptors and C-ABL Inhibitors: A New Therapeutic Approach for Parkinson's Disease.

Priya P Shejul, Gaurav M Doshi
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Abstract

Parkinson's disease (PD) is the second-most prevalent central nervous system (CNS) neurodegenerative condition. Over the past few decades, suppression of BCR-Abelson tyrosine kinase (c-Abl), which serves as a marker of -synuclein aggregation and oxidative stress, has shown promise as a potential therapy target in PD. c-Abl inhibition has the potential to provide neuroprotection against PD, as shown by experimental results and the first-in-human trial, which supports the strategy in bigger clinical trials. Furthermore, glutamate receptors have also been proposed as potential therapeutic targets for the treatment of PD since they facilitate and regulate synaptic neurotransmission throughout the basal ganglia motor system. It has been noticed that pharmacological manipulation of the receptors can change normal as well as abnormal neurotransmission in the Parkinsonian brain. The review study contributes to a comprehensive understanding of the approach toward the role of c-Abl and glutamate receptors in Parkinson's disease by highlighting the significance and urgent necessity to investigate new pharmacotherapeutic targets. The article covers an extensive insight into the concept of targeting, pathophysiology, and c-Abl interaction with α-synuclein, parkin, and cyclin-dependent kinase 5 (Cdk5). Furthermore, the concepts of Nmethyl- D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA) receptor, and glutamate receptors are discussed briefly. Conclusion: This review article focuses on in-depth literature findings supported by an evidence-based discussion on pre-clinical trials and clinical trials related to c-Abl and glutamate receptors that act as potential therapeutic targets for PD.

谷氨酸受体和 C-ABL 抑制剂:帕金森病的新治疗方法。
帕金森病(PD)是发病率第二高的中枢神经系统(CNS)神经退行性疾病。在过去的几十年中,作为突触核蛋白聚集和氧化应激标志物的BCR-Abelson酪氨酸激酶(c-Abl)的抑制已显示出作为帕金森病潜在治疗靶点的前景。正如实验结果和首次人体试验所显示的那样,c-Abl抑制具有对帕金森病提供神经保护的潜力,这为更大范围的临床试验提供了支持。此外,谷氨酸受体也被认为是治疗帕金森病的潜在治疗靶点,因为它们能促进和调节整个基底节运动系统的突触神经传递。人们已经注意到,对受体进行药理操作可以改变帕金森患者大脑中正常和异常的神经传递。这篇综述有助于全面了解 c-Abl 和谷氨酸受体在帕金森病中的作用,突出了研究新的药物治疗靶点的重要性和迫切性。文章对靶向概念、病理生理学以及c-Abl与α-突触核蛋白、parkin和细胞周期蛋白依赖性激酶5(Cdk5)之间的相互作用进行了广泛深入的探讨。此外,还简要讨论了 N-甲基-D-天冬氨酸(NMDA)、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPA)和谷氨酸受体的概念。结论这篇综述文章着重于深入的文献研究结果,并以证据为基础讨论了与c-Abl和谷氨酸受体有关的临床前试验和临床试验,这些受体是治疗帕金森病的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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