Ask about this productRelated genes to: Dyrk1a antibody
- Gene:
- DYRK1A NIH gene
- Name:
- dual specificity tyrosine phosphorylation regulated kinase 1A
- Previous symbol:
- DYRK1, DYRK, MNBH
- Synonyms:
- -
- Chromosome:
- 21q22.13
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-29
- Date modifiied:
- 2016-02-12
Related products to: Dyrk1a antibody
Related articles to: Dyrk1a antibody
- Type 1 conventional dendritic cells (cDC1s) play an integral role in mediating immune responses and maintaining homeostasis, yet the molecular mechanisms underlying their functions remain poorly understood. In this study, we identified dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) as a key kinase that responded to TLR and growth factor stimulation and acted as an essential regulator of cDC1 function. Genetic ablation of Dyrk1a specifically in cDC1s impaired antitumor immunity and accelerated tumor progression in murine models. Mechanistically, DYRK1A mediated the phosphorylation of the mTORC1 inhibitor TSC2 at serine 540, triggering the degradation of TSC2 and promoting the mTORC1 signaling in cDC1s. Notably, Tsc2 deletion in Dyrk1a-deficient cDC1s remarkably restored their antitumor immune functions. Furthermore, DYRK1A-mediated mTORC1 signaling in cDC1s positively correlated with effector T-cell responses across multiple human cancers. Our findings highlight a critical role for the DYRK1A-TSC2-mTORC1 signaling pathway in regulating cDC1 functions in antitumor immunity, offering potential strategies to improve cancer immunotherapy. - Source: PubMed
Publication date: 2026/04/23
Wang HongjiaoJiang HeHe SonglinRen SongwenLi HaiwenLiu WangnanZhou ChunyunZhu PanChen KerenCao WeijiaQin YanDu DanXiao NengmingHuang HonglingKo Chun-JungZheng YimingWang BoZou QiangShi Jian-HongLi XunJie Zuliang - Alzheimer's disease (AD) is a debilitating neurodegenerative condition characterized by progressive cognitive impairment, memory deterioration, and neuronal dysfunction. Its complex pathophysiology involves multiple interlinked processes, including amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, synaptic dysfunction, and cholinergic deficits. Current FDA-approved therapies provide only symptomatic relief and fail to halt disease progression, highlighting the urgent need for more effective treatment strategies. This review provides a comprehensive overview of the pathological mechanisms underlying AD and the emerging therapeutic targets for the design of tractable anti-AD scaffolds, namely, acetylcholinesterase, beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), glycogen synthase kinase-3β (GSK3β), dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), histone deacetylases (HDACs), and soluble epoxide hydrolase (sEH). Emphasis is placed on the paradigm shift from single-target therapies to multitarget-directed ligands (MTDLs), which are increasingly recognized as promising tools to tackle AD's multifactorial pathology. We also discuss recent advances in medicinal chemistry and structure-guided drug discovery campaigns aimed at developing pharmacologically optimized, BBB-penetrant MTDLs. By consolidating mechanistic insights with therapeutic innovation, this review aims to facilitate the development of next-generation therapeutics with enhanced efficacy and disease-modifying potential in AD. - Source: PubMed
Publication date: 2026/04/19
Thakur AmandeepRana MandeepVanjani SakshiLiou Kei-ChiTaliyan RajeevNepali KunalYang Chih-Hao - Tauopathies arise when normal functions of the tau protein in axonal transport and neuronal maintenance are disrupted by an imbalance between kinases and phosphatases. Dysregulation of key kinases such as dual-specificity Tyrosine-Regulated Kinase 1A (DYRK1A), Tau Tubulin Kinase 1 (TTBK1), and ABL Proto-Oncogene 1, and Non-Receptor Tyrosine Kinase (ABL1) drives excessive tau phosphorylation and neurofibrillary tangle accumulation. DYRK1A regulates MAPT exon 10 splicing and phosphorylates tau at multiple Ser/Thr residues, priming it for further phosphorylation by other kinases. TTBK1 phosphorylates tau at disease-associated epitopes within the microtubule-binding domain, promoting detachment from microtubules and aggregation. ABL1 phosphorylates tau at tyrosine residues, linking tau modification with Aβ-induced synaptic dysfunction. These events collectively drive tau hyperphosphorylation, misfolding, and neurofibrillary pathology characteristic of tauopathies. To identify natural product-derived multitarget inhibitors for these kinases, we developed a comprehensive machine learning (ML) workflow trained on bioactivity data from ChEMBL and BindingDB. We implemented five distinct classifiers: CatBoost, Support Vector Machine (SVM), k-Nearest Neighbors (KNN), Naive Bayes, and XGBoost. Stratified sampling and SMOTE were employed to address class imbalance for DYRK1A and ABL1, while Bemis-Murcko scaffold splitting was used to ensure rigorous evaluation of the data-scarce TTBK1 data set. A soft-voting ensemble model, integrating optimized CatBoost, XGBoost, and SVM, demonstrated superior performance. This robust ensemble was deployed to screen ∼695,000 natural compounds from the COCONUT 2.0 database. The resulting hits were refined through consensus molecular docking and deep learning-based rescoring (GNINA), leading to the identification of two high-potential lead molecules, CNP0591834.1 and CNP0484145.0. Validation using 1 μs molecular dynamics simulations confirmed their conformational stability and strong binding affinities. Steered MD further demonstrated their superior mechanical resistance to unbinding, particularly in DYRK1A and ABL1 complexes. Overall, this integrative computational framework highlights these two natural compounds as potent multitarget leads with strong potential to mitigate tau-hyperphosphorylation-driven neurodegeneration. - Source: PubMed
Publication date: 2026/04/17
Choudhury ArunabhSaeed Mohammad UmarPrabha SnehHassan Md Imtaiyaz - 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. - Source: PubMed
Publication date: 2026/04/14
Meijer LaurentLindberg Mattias FHogrel GaëlleKhor Bernard - Autism spectrum disorder (ASD) is a neurodevelopmental condition that occurs in early childhood, characterized by a broad range of clinical manifestations and impairments in social communication. It represents one of the most prevalent neurodevelopmental disorders, affecting approximately 1% of the general population. The phenotypic heterogeneity of ASD arises from different genetic causes, including chromosomal abnormalities, copy number variants (CNVs), and single-nucleotide variants (SNVs), which may occur as de novo or inherited events. Moreover, the polygenic and multifactorial nature of ASD, together with epigenetic regulation and environmental influences, contributes substantially to its complex genetic architecture. Molecular diagnosis remains challenging and relies on multiple genomic approaches, such as array comparative genomic hybridization (array-CGH), whole-exome sequencing (WES), and whole-genome sequencing (WGS); however, the diagnostic yields of these methods remain limited, reflecting the complexity of ASD's genetic architecture. Notably, ASD-associated genes converge on key biological pathways, particularly those involved in transcriptional regulation, chromatin remodeling, synaptic function, and neuronal signaling. These include well-established risk genes such as , , , , , , , , and , among others. This review summarizes the current knowledge on the genetic basis of ASD, highlighting key aspects of its complex genetic architecture. By integrating evidence from major clinical and research databases, it provides a clearer understanding of the underlying mechanisms, supporting improved diagnosis and future research and therapeutic strategies. - Source: PubMed
Publication date: 2026/04/04
Treccarichi SimoneVinci MirellaVirgillito MiriamMusumeci AntoninoBruno FrancescaPapa CarlaGalati Rando RosannaMarano PietroGreco DonatellaFallea AntonioBrancato DesireeCalì SiriaGarcia GresheenFederico ConcettaSaccone SalvatoreCalì Francesco