更新于：2024-11-01

DYRK x NGF

更新于：2024-11-01

基本信息

关联

项与 DYRK x NGF 相关的药物

NNI-351

靶点

DYRK x NGF

作用机制

DYRK抑制剂 [+1]

在研机构-

原研机构

NeuroNascent, Inc.

在研适应症-

非在研适应症

注意缺陷障碍伴多动 [+3]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 DYRK x NGF 相关的临床结果

登录后查看更多信息

100 项与 DYRK x NGF 相关的转化医学

登录后查看更多信息

0 项与 DYRK x NGF 相关的专利（医药）

登录后查看更多信息

项与 DYRK x NGF 相关的文献（医药）

2013-09-01·CNS Drugs2区 · 医学

Prospects for Improving Brain Function in Individuals with Down Syndrome

2区 · 医学

Review

作者: Alberto C. S. Costa ; Jonah J. Scott-McKean

Down syndrome (DS), which results from an extra copy of chromosome 21 (trisomy 21), is the most common genetically defined cause of intellectual disability. Although no pharmacotherapy aimed at counteracting the cognitive and adaptive deficits associated with this genetic disorder has been approved at present, there have been several new promising studies on pharmacological agents capable of rescuing learning/memory deficits seen in mouse models of DS. Here, we will review the available mouse models for DS and provide a comprehensive, albeit not exhaustive review of the following preclinical research strategies: (1) SOD1 and antioxidant agents; (2) APP and γ-secretase inhibitors; (3) DYRK1A and the polyphenol epigallocatechin gallate (EGCG); (4) GIRK2 and fluoxetine; (5) adrenergic receptor agonists; (6) modulation of GABAA and GABAB receptors; (7) agonism of the hedgehog signaling pathway; (8) nerve growth factor (NGF) and other neurotrophic factors; (9) anticholinesterase (AChE) agents; and (10) antagonism of NMDA receptors. Finally, we will review briefly five different strategies in DS that have led to clinical studies that either have been concluded or are currently underway: (1) antioxidant therapy; (2) AChE therapy; (3) green tea extract therapy; (4) RG1662 therapy; and (5) memantine therapy. These are exciting times in DS research. Within a decade or so, it is well into the realm of possibility that new forms of pharmacotherapies might become valuable tools in the armamentarium of developmental clinicians, as adjutants to more traditional and proven forms of habilitative interventions aimed at improving the quality of life of individuals with DS.

2005-08-01·Molecular Biology of the Cell3区 · 生物学

DYRK1A Enhances the Mitogen-activated Protein Kinase Cascade in PC12 Cells by Forming a Complex with Ras, B-Raf, and MEK1

3区 · 生物学

Article

作者: Rahmani, Zohra ; Kelly, Paul A.

Dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A) is the human homologue of the Drosophila mnb (minibrain) gene. In Drosophila, mnb is involved in postembryonic neurogenesis. In human, DYRK1A maps within the Down syndrome critical region of chromosome 21 and is overexpressed in Down syndrome embryonic brain. Despite its potential involvement in the neurobiological alterations observed in Down syndrome patients, the biological functions of the serine/threonine kinase DYRK1A have not been identified yet. Here, we report that DYRK1A overexpression potentiates nerve growth factor (NGF)-mediated PC12 neuronal differentiation by up-regulating the Ras/MAP kinase signaling pathway independently of its kinase activity. Furthermore, we show that DYRK1A prolongs the kinetics of ERK activation by interacting with Ras, B-Raf, and MEK1 to facilitate the formation of a Ras/B-Raf/MEK1 multiprotein complex. These data indicate that DYRK1A may play a critical role in Ras-dependent transducing signals that are required for promoting or maintaining neuronal differentiation and suggest that overexpression of DYRK1A may contribute to the neurological abnormalities observed in Down syndrome patients.

Frontiers in Aging Neuroscience

Network pharmacology identify intersection genes of quercetin and Alzheimer’s disease as potential therapeutic targets

Article

作者: Li, Cheng ; Chen, Wenzhi ; Zhu, Yu ; Xu, Renshi ; Wei, Caihui ; Li, Shu

BackgroundCurrently, there are no efficient therapies for Alzheimer’s disease (AD) among the elderly, although it is the most common etiology of dementia among the elderly. Quercetin, which has a variety of therapeutic properties, may pave the way for novel approaches to AD treatment. In the AD patients’ frontal cortex, current study aims to identify the potential mechanisms of quercetin’s pharmacological targets.Materials and methodsThe pharmacological targets of quercetin have been studied from DrugBank and SwissTarget. In order to distinguish AD-associated genes targeted by quercetin (Q-ADGs), we utilized an integrated intersection of gene expressions of the frontal cortex in combination with transcriptome analysis. To detect cortex-related Q-ADGs and immune-related Q-ADGs, a drug screening database and the immune infiltration analysis was utilized. The Q-ADGs were then linked with the AD severity scores (MMSE scores) to find severity-associated Q-ADGs. In addition, the miRNA-seq datasets were examined to identify severity-associated Q-ADG-miRNAs. Twelve genes, more frequently related to AD by previous studies among all the genes identified in the present study, were subjected to the verification of qRT-PCR in AD cell model.ResultsIn the frontal lobe of AD, 207 Q-ADGs were discovered and found that axonogenesis, glial differentiation, and other biological processes had been enriched. There were 155 immune-related Q-ADGs (e.g., COX2, NOS2, HMGB1) and 65 cortex-related Q-ADGs (e.g., FOXO1, CXCL16, NOTCH3). Sixteen Q-ADGs (e.g., STAT3, RORA, BCL6) and 28 miRNAs (e.g., miR-142-5p, miR-17-5p) were found to be related to MMSE scores. In the qRT-PCR results, six out of twelve genes were significantly regulated by quercetin. DYRK1A, FOXO1, NOS2, NGF, NQO1, and RORA genes were novel target of quercetin in AD. DYRK1A, NOS2, and NQO1 genes targeted by quercetin have benefits in the treatment of AD. However, FOXO1, NGF, and RORA genes targeted by quercetin might have a negative impact on AD.ConclusionThe role of quercetin in AD appears to be multifaceted, and it can affect patients’ frontal cortex in a variety of pathways, such as axonogenesis, immune infiltration, and glial cell differentiation. DYRK1A, NOS2, and NQO1 might be potential novel effective drug targets for quercetin in AD.