DYRK1A and Parkinson's disease, facts and hypotheses.

IF 5.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Disease Pub Date : 2026-04-14 DOI:10.1016/j.nbd.2026.107379

Laurent Meijer, Mattias F Lindberg, Gaëlle Hogrel, Bernard Khor

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引用次数: 0

Abstract

The dual-specificity, tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is intensively studied because of its implication in numerous human diseases (Down syndrome, Alzheimer's disease, type 2 diabetes, myocardial infarction, various cancers and leukaemia, etc.). Several GWAS studies have identified DYRK1A as a risk factor for Parkinson's disease (PD). DYRK1A indeed phosphorylates at least 20 proteins clearly involved in PD: AMPH, CASP9, DYN1, FOXO, GSK3B, MAP1B, MAPT, MEF2D, NFAT, TP53, PRKN, PLK2, RABs, RCAN1, SEPT4, SNCA, STAT3, SYNJ1, TOM70, WASL. Several other proteins involved in PD interact with DYRK1A: calpains, DSCAM, REST/NRSF, 14-3-3. DYRK1A is involved in axonal transport, neural stem cells proliferation and differentiation, and neuroinflammation. A few DYRK1A inhibitors have been tested on PD models, generally showing protective effects. The overall picture provided by this comprehensive review on the links between DYRK1A and PD advocates for more fundamental studies to understand how DYRK1A participates to the onset and development of PD and dementia with Lewy bodies (DLB), two closely related disorders. It also encourages the evaluation of well-characterized pharmacological modulators of DYRK1A as therapeutic approaches to various aspects of PD and DLB.

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DYRK1A和帕金森病，事实和假设。

双特异性酪氨酸磷酸化调节激酶1A （DYRK1A）被广泛研究，因为它与许多人类疾病（唐氏综合征、阿尔茨海默病、2型糖尿病、心肌梗死、各种癌症和白血病等）有关。几项GWAS研究已经确定DYRK1A是帕金森病（PD）的危险因素。DYRK1A确实磷酸化了至少20种与PD相关的蛋白：AMPH、CASP9、DYN1、FOXO、GSK3B、MAP1B、MAPT、MEF2D、NFAT、TP53、PRKN、PLK2、RABs、RCAN1、SEPT4、SNCA、STAT3、SYNJ1、TOM70、WASL。PD与DYRK1A相互作用的其他几个蛋白：calpains， DSCAM, REST/NRSF, 14-3-3。DYRK1A参与轴突转运、神经干细胞增殖和分化以及神经炎症。一些DYRK1A抑制剂已经在PD模型上进行了测试，一般显示出保护作用。这篇关于DYRK1A与PD之间联系的综合综述提供了一个整体的图景，提倡进行更多的基础研究，以了解DYRK1A如何参与PD和路易体痴呆（DLB）这两种密切相关的疾病的发生和发展。它还鼓励对DYRK1A的药理调节剂进行评估，以作为PD和DLB各方面的治疗方法。

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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来源期刊

Neurobiology of Disease 医学-神经科学

CiteScore

11.20

自引率

3.30%

发文量

270

审稿时长

76 days

期刊介绍： Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.