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Krüppel 样因子 4 的治疗靶点及其在帕金森病中的药理作用:全面综述。

Therapeutic Targeting of Krüppel-Like Factor 4 and Its Pharmacological Potential in Parkinson's Disease: a Comprehensive Review.

机构信息

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, 6718773654, Iran.

Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, 6718773654, Iran.

出版信息

Mol Neurobiol. 2024 Jun;61(6):3596-3606. doi: 10.1007/s12035-023-03800-2. Epub 2023 Nov 24.

Abstract

Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is found in different human tissues and shows diverse regulatory activities in a cell-dependent manner. In the brain, KLF4 controls various neurophysiological and neuropathological processes, and its contribution to various neurological diseases has been widely reported. Parkinson's disease (PD) is an age-related neurodegenerative disease that might have a connection with KLF4. In this review, we discussed the potential implication of KLF4 in fundamental molecular mechanisms of PD, including aberrant proteostasis, neuroinflammation, apoptosis, oxidative stress, and iron overload. The evidence collected herein sheds new light on KLF4-mediated pathways, which manipulation appears to be a promising therapeutic target for PD management. However, there is a gap in the knowledge on this topic, and extended research is required to understand the translational value of the KLF4-oriented therapeutical approach in PD.

摘要

Krüppel 样因子 4(KLF4)是一种锌指转录因子,存在于不同的人体组织中,并以细胞依赖的方式表现出不同的调节活性。在大脑中,KLF4 控制着各种神经生理和神经病理过程,其对各种神经疾病的贡献已被广泛报道。帕金森病(PD)是一种与年龄相关的神经退行性疾病,可能与 KLF4 有关。在这篇综述中,我们讨论了 KLF4 在 PD 的基本分子机制中的潜在意义,包括异常的蛋白质稳态、神经炎症、细胞凋亡、氧化应激和铁过载。本文收集的证据为 KLF4 介导的途径提供了新的见解,其调控似乎是 PD 管理的有前途的治疗靶点。然而,在这一主题的知识方面存在差距,需要进一步的研究来理解 KLF4 导向治疗方法在 PD 中的转化价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1731/11087351/3c2bd85fa24a/12035_2023_3800_Fig1_HTML.jpg

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