CDK5 (Cyclin Dependent Kinase 5)

The neuroectodermal rosettes were then treated with and without LiCl (Cdk5 inhibitor) or roscovitine (GSK-3β inhibitor) and assayed for the expression of tau, P-tau, nestin (an early marker of neurogenesis), Cdk5 and GSK-3β. These preliminary results suggest that progesterone induces tau expression and its phosphorylation during the differentiation of neuroectodermal rosettes from hESC and suggest that tau and its phosphorylation is obligatory for neuronal precursor cell mitosis. The parallels between neural embryogenesis and neurodegeneration are discussed in the context of tau phosphorylation and the aberrant re-entry of neurons into the cell cycle in AD.

Western blotting validated downregulation of CDK5, NFKB1, and PTGS2, aligning with computational predictions. These findings highlight selective, multi-targeted anticancer activity of cosmosiin, particularly through PTGS2, NFKB1, and CDK5, supporting its therapeutic potency for breast cancer with favorable effects on apoptosis, proliferation, and cell migration, while correlating with survival and immune infiltration outcomes.

Furthermore, the combination of LIMK1 and CDK5 inhibitors significantly suppresses metastasis in multiple models. This work highlights LIMK1 as a novel regulatory and targetable kinase of β-catenin, informing the treatment of advanced cancer.

Gemcitabine-based chemotherapy remains the cornerstone for advanced PDAC...Additionally, these functions can be significantly inhibited by pharmacological inhibition (roscovitine) or genetic ablation of CDK5...Increased expression of CDK5, USP32, and Rap1 is significantly associated with poorer prognosis in PDAC. We identified the previously unrecognized oncogenic function and clinical importance of the CDK5-USP32-Rap1 axis, providing preclinical evidence for potential new combination strategies for PDAC therapy.

Immunohistochemistry analysis of TC samples further confirmed that increased CDK5 and reduced p21 expression were associated with more advanced tumor stages and aggressive phenotypes. These findings suggested that CDK5‑mediated degradation of p21 contributes to TC progression and malignancy, highlighting the potential of targeting the CDK5‑p21 axis as a therapeutic strategy for management of TC.

CDK5 knockdown partially attenuated the ATG9B-4-induced increase in proliferation and migration in liver cancer cells. ATG9B-4 deteriorated the proliferation and migration of liver cancer cells in an ARNTL-CDK5 pathway-dependent manner.

It repressed the release of mitochondrial cytochrome c and apoptosis-inducing factor (AIF) to hinder caspase-dependent and caspase-independent apoptotic neuronal death. Oxytocin could be a promising candidate for HD management by hampering both mitochondrial and non-mitochondrial apoptosis through inhibition of calpain-2/p25 Cdk5/MEF-2 pathway.

In addition, we used the ScircRNA inhibiting CDK5 expression to trigger T-cell mediated cancer immunotherapy for treating prostate cancer in vivo. The ScircRNAs possessed the advantages of stable structure and simple construction, and can specifically inhibit the function of target miRNAs, which has a potential therapeutic application prospect in prostate cancer.

We have also elucidated the underlying genetic characteristics of glioma with gene fusions. Collectively, our findings have the potential to inform future clinical treatment strategies for patients with glioma.

In SH-SY5Y cells, knockdown of all isoforms of CD59 including IRIS-1 and 2 not only elevates phosphorylated tau but also increases cyclin-dependent kinase 5 (CDK5) expression, known promoter of hyperphosphorylation and accumulation of tau, a key pathological feature of AD. Additionally, we found that prolonged exposure to high glucose or cytokines markedly reduces the expression of IRIS-1 and 2 in SH-SY5Y cells, suggesting a link between AD pathology and metabolic stress through modulation of these isoforms.

Our multi-omic analysis provides new insight into molecular underpinnings of CHOL and identifies candidate disease drivers, signaling pathways and herbal targets for further validation. This systematic approach established a framework for illuminating causal links between genetics, molecular mechanisms and disease pathogenesis, with potential to accelerate drug and biomarker development for CHOL.

N-acetylcysteine (NAC), roscovitine and Mdivi-1 ameliorated SE-induced PV neuronal degeneration by mitigating CDK5 Y15 hyperphosphorylation, aberrant mitochondrial fragmentation and reduced GPx1-mediated NF-κB inhibition. Furthermore, SN50 (a NF-κB inhibitor) alleviated SE-induced PV neuronal degeneration, independent of dysregulation of mitochondrial fission, CDK5 hyperactivation and GPx1 downregulation. These findings provide an evidence that oxidative stress may activate CDK5-DRP1- and GPx1-NF-κB-mediated signaling pathways, which would be possible therapeutic targets for preservation of PV neurons in various diseases.