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新型双重特异性酪氨酸磷酸化调节激酶1A(DYRK1A)抑制剂可挽救唐氏综合征小鼠模型的学习和记忆缺陷。

Novel DYRK1A Inhibitor Rescues Learning and Memory Deficits in a Mouse Model of Down Syndrome.

作者信息

Stensen Wenche, Rothweiler Ulli, Engh Richard Alan, Stasko Melissa R, Bederman Ilya, Costa Alberto C S, Fugelli Anders, Svendsen John S Mjøen

机构信息

Department of Chemistry, UiT, The Arctic University of Norway, 9037 Tromsø, Norway.

Pharmasum Therapeutics AS, Gaustadalleen 21, 0349 Oslo, Norway.

出版信息

Pharmaceuticals (Basel). 2021 Nov 17;14(11):1170. doi: 10.3390/ph14111170.

Abstract

Down syndrome (DS) is a complex genetic disorder associated with substantial physical, cognitive, and behavioral challenges. Due to better treatment options for the physical co-morbidities of DS, the life expectancy of individuals with DS is beginning to approach that of the general population. However, the cognitive deficits seen in individuals with DS still cannot be addressed pharmacologically. In young individuals with DS, the level of intellectual disability varies from mild to severe, but cognitive ability generally decreases with increasing age, and all individuals with DS have early onset Alzheimer's disease (AD) pathology by the age of 40. The present study introduces a novel inhibitor for the protein kinase DYRK1A, a key controlling kinase whose encoding gene is located on chromosome 21. The novel inhibitor is well characterized for use in mouse models and thus represents a valuable tool compound for further DYRK1A research.

摘要

唐氏综合征(DS)是一种复杂的遗传疾病,伴有严重的身体、认知和行为挑战。由于对DS身体合并症有了更好的治疗选择,DS患者的预期寿命开始接近普通人群。然而,DS患者出现的认知缺陷仍无法通过药物治疗解决。在年轻的DS患者中,智力残疾程度从轻度到重度不等,但认知能力通常会随着年龄增长而下降,并且所有DS患者在40岁时都会出现早发性阿尔茨海默病(AD)病理特征。本研究介绍了一种针对蛋白激酶DYRK1A的新型抑制剂,DYRK1A是一种关键的调控激酶,其编码基因位于21号染色体上。这种新型抑制剂在小鼠模型中的应用已得到充分表征,因此是进一步研究DYRK1A的有价值的工具化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/797f/8617627/182e5823e46f/pharmaceuticals-14-01170-g001.jpg

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