Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Pharmacol Res. 2020 Oct;160:105090. doi: 10.1016/j.phrs.2020.105090. Epub 2020 Jul 21.
Aging is known to be one of the major risk factors in many neurodegenerative diseases (ND) whose prevalence is estimated to rise in the coming years due to the increase in life expectancy. Examples of neurodegenerative diseases include Huntington's, Parkinson's, and Alzheimer's diseases, along with Amyotrophic Lateral Sclerosis, Spinocerebellar ataxias and Frontotemporal Dementia. Given that so far these ND do not have effective pharmacological therapies, a better understanding of the molecular and cellular mechanisms can contribute to development of effective treatments. During the previous decade, the data indicated that dysregulation of MAP kinases [which included c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p38] are associated with several stages of the inflammatory process which in turn contributes to age-related neurodegenerative diseases. This evidence suggests that control of inflammation through regulation of MAP kinase could be a worthwhile approach against neurodegenerative diseases. In this review we summarize the pathways of MAP kinase signal transduction and different pharmacological inhibitors that can be used in its modulation against ND.
衰老是许多神经退行性疾病（ND）的主要危险因素之一，由于预期寿命的延长，这些疾病的患病率预计在未来几年将会上升。神经退行性疾病的例子包括亨廷顿氏病、帕金森氏病和阿尔茨海默氏病，以及肌萎缩侧索硬化症、脊髓小脑共济失调和额颞叶痴呆症。鉴于到目前为止，这些 ND 没有有效的药物治疗方法，更好地了解分子和细胞机制有助于开发有效的治疗方法。在过去的十年中，数据表明 MAP 激酶[包括 c-Jun N-末端激酶（JNK）、细胞外信号调节激酶 1 和 2（ERK1/2）和 p38]的失调与炎症过程的几个阶段有关，而炎症过程反过来又导致与年龄相关的神经退行性疾病。这一证据表明，通过调节 MAP 激酶来控制炎症可能是对抗神经退行性疾病的一种有价值的方法。在这篇综述中，我们总结了 MAP 激酶信号转导的途径以及可以用于调节 ND 的不同药理学抑制剂。
