揭示 AKT/ERK 级联及其在帕金森病中的作用。

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-08-13 DOI:10.1007/s00204-024-03829-9
Priyanka Kumari Keshri, Surya Pratap Singh
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引用次数: 0

摘要

帕金森病给全球医疗系统造成了巨大且日益沉重的负担,因此有必要深入了解其潜在的分子机制,以开发有效的治疗方法。AKT 和 ERK 通路在帕金森病中发挥着至关重要的作用,它们影响着支持神经元存活的多种细胞通路。研究人员在揭示这些通路如何受上游激酶控制以及它们的下游效应如何促进细胞信号传导方面取得了显著进展。然而,随着我们对其复杂性的深入研究,我们遇到了越来越复杂的问题,多种信号通路的交汇使问题变得更加复杂。激酶的许多靶点与其他激酶的靶点重叠,它们不仅影响特定底物,还影响整个信号网络。本综述以帕金森病为背景,探讨了 AKT/ERK 通路与其他几种信号级联之间错综复杂的相互作用,包括氧化应激、内质网应激、钙稳态、炎症和自噬。我们讨论了这些通路的失调如何导致疾病进展和神经元功能障碍,并强调了潜在的干预治疗靶点。通过阐明 AKT/ERK 通路与其他信号级联之间复杂的相互作用网络,本综述旨在深入探讨帕金森病的发病机制,并描述新型治疗策略的发展。
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Unraveling the AKT/ERK cascade and its role in Parkinson disease

Parkinson disease represents a significant and growing burden on global healthcare systems, necessitating a deeper understanding of their underlying molecular mechanisms for the development of effective treatments. The AKT and ERK pathways play crucial roles in the disease, influencing multiple cellular pathways that support neuronal survival. Researchers have made notable progress in uncovering how these pathways are controlled by upstream kinases and how their downstream effects contribute to cell signalling. However, as we delve deeper into their intricacies, we encounter increasing complexity, compounded by the convergence of multiple signalling pathways. Many of their targets overlap with those of other kinases, and they not only affect specific substrates but also influence entire signalling networks. This review explores the intricate interplay of the AKT/ERK pathways with several other signalling cascades, including oxidative stress, endoplasmic reticulum stress, calcium homeostasis, inflammation, and autophagy, in the context of Parkinson disease. We discuss how dysregulation of these pathways contributes to disease progression and neuronal dysfunction, highlighting potential therapeutic targets for intervention. By elucidating the complex network of interactions between the AKT/ERK pathways and other signalling cascades, this review aims to provide insights into the pathogenesis of Parkinson disease and describe the development of novel therapeutic strategies.

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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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