Role and Therapeutic Potential of RAGE Signaling in Neurodegeneration.
Role and Therapeutic Potential of RAGE Signaling in Neurodegeneration.
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DOI：
10.2174/1389450123666220610171005
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发表时间：
2022
影响因子：
3.2
通讯作者：
Pehar, Mariana
中科院分区：
文献类型：
--
作者：
Kinscherf, Noah Alexander;Pehar, Mariana
关键词：
晚期糖基化终末产物受体（AGEs）的激活已被证明在多种神经退行性疾病的发展中起积极作用，包括阿尔茨海默病、帕金森病和肌萎缩性侧索硬化症。虽然最初被鉴定为晚期糖基化终产物的受体，但它是一种能够结合多种配体的模式识别受体。信号转导的最终结果在特定的环境和细胞类型中定义，并且可以发挥神经毒性和神经保护功能。对信号传导网络的复杂性有贡献的是，已经描述了具有独特信号传导能力的不同的信号传导亚型。此外，多种β-受体配体结合其他受体，β-受体拮抗作用可显著影响它们的信号传导。在这里，我们讨论了神经退行性病变的细胞类型特异性β信号转导的结果。此外，我们将审查已开发的不同方法，以靶向信号转导及其治疗潜力。清楚地了解以细胞类型和疾病特异性方式进行信号转导的结果将有助于推进靶向EGFR的新疗法的开发。对抗RAGE神经毒性信号传导同时保留其神经保护作用的能力对于针对RAGE信号传导的新型疗法的成功至关重要。这篇综述探讨了在神经退行性疾病中，β-淀粉样蛋白信号传导的有益和有害影响。已经开发了几种方法来靶向具有治疗目的的信号传导。策略，特别是抵消干扰信号的有害影响，同时保留其潜在的有益效果将需要利用其治疗潜力。
Activation of the receptor for advanced glycation end products (RAGE) has been shown to play an active role in the development of multiple neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis. Although originally identified as a receptor for advanced glycation end products, RAGE is a pattern recognition receptor able to bind multiple ligands. The final outcome of RAGE signaling is defined in a context and cell type specific manner and can exert both neurotoxic and neuroprotective functions. Contributing to the complexity of the RAGE signaling network, different RAGE isoforms with distinctive signaling capabilities have been described. Moreover, multiple RAGE ligands bind other receptors and RAGE antagonism can significantly affect their signaling. Here, we discuss the outcome of cell-type specific RAGE signaling in neurodegenerative pathologies. In addition, we will review the different approaches that have been developed to target RAGE signaling and their therapeutic potential. A clear understanding of the outcome of RAGE signaling in a cell type- and disease-specific manner would contribute to advance the development of new therapies targeting RAGE. The ability to counteract RAGE neurotoxic signaling while preserving its neuroprotective effects would be critical for the success of novel therapies targeting RAGE signaling. This review examines the beneficial and detrimental effects of RAGE signaling in neurodegenerative conditions. Several methods have been developed to target RAGE signaling with therapeutic purposes. Strategies to specifically counteract RAGE signaling-detrimental effects while preserving its potential beneficial effects would be needed to harness their therapeutic potential.
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影响因子：
3.3
作者：
Daborg, Jonny;von Otter, Malin;Sjolander, Annica;Nilsson, Staffan;Minthon, Lennart;Gustafson, Deborah R.;Skoog, Ingmar;Blennow, Kaj;Zetterberg, Henrik
通讯作者：
Zetterberg, Henrik
DOI：
10.1097/01.jnen.0000179050.54522.5a
发表时间：
2005-09-01
影响因子：
3.2
作者：
Dalfó, E;Portero-Otín, M;Ferrer, I
通讯作者：
Ferrer, I
影响因子：
82.9
作者：
Deane, R;Yan, SD;Zlokovic, B
通讯作者：
Zlokovic, B
影响因子：
3.7
作者：
C RC;Lukose B;Rani P
通讯作者：
Rani P
影响因子：
3.7
作者：
Di Maggio, Stefania;Gatti, Elena;Raucci, Angela
通讯作者：
Raucci, Angela