CNR1 (Cannabinoid Receptor 1)

Rescue experiments confirmed that CNR1 overexpression reversed the protective effects of WTAPP1 knockdown on high-glucose-induced damage in HTR-8/Svneo cells, while NF-κB inhibition by BAY-11-7085 attenuated high glucose-induced damage. This study unveils a novel WTAPP1/WTAP-m6A-CNR1-NF-κB axis driving trophoblast cell injury in GDM, highlighting WTAPP1 as a potential therapeutic target for hyperglycemia-induced placental injury.

Importantly, the CB1 receptor antagonist AM251, but not CB2 antagonist AM630, blocked the beneficial effects of CBD on performance in object location and social tasks in STZ-treated rats, highlighting CB1 receptor activation as a key mechanism. These findings suggest that CBD holds promise as a therapeutic agent for inflammation-induced AD, with the potential to ameliorate cognitive deficits and prevent disease onset through mechanisms involving CB1 receptor activation and modulation of neuroinflammation.

This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.

Tamibarotene, a synthetic retinoid used in the treatment of acute promyelocytic leukemia, has been reported to induce differentiation in the SH-SY5Y cell line into neurons. Inhibition of the PI3K/Akt signaling pathway using LY294002 resulted in a decreased efficacy of AM80-induced differentiation in SH-SY5Y cells, along with downregulation of neuronal marker expression. These findings suggest that Am80 can effectively promote the differentiation of SH-SY5Y cells into neurons and reduce the proliferation of neuroblastoma cells, which is related to the PI3K/AKT pathway, providing a good model for the study of nervous system diseases.

The model containing CNR1, PRKACB, CDKN3, and PCLAF can serve as a new prognostic biomarker for predicting the prognosis of patients with neuroblastoma. Findings on immune cell infiltration and immune checkpoints provide novel insights for the immunotherapy of neuroblastoma.

Furthermore, CNR1 gene expression levels are larger in WERI-ETOR cells than those in WERI-Rb1 cells. Therefore, the development of etoposide insensitivity may be associated with rises in CNR1 gene expression, which in turn suppress TRPM8 gene expression through crosstalk.

In particular, we identified the role of Cnr1 expressed in microglia for mediating its gene-environment effect on adolescent mPFC maturation and adult social memory in 16p11dup mice. We are currently investigating molecular mechanisms of how adolescent THC treatment impair microglia-mediated mPFC maturation in a neuronal subtype-specific manner.

In an attempt to further explore the role of FAM in CLL immune regulation, the expression characteristics of LPL, SOCS3, and CNR1 at the single-cell level were analyzed in CLL patient samples before and after ibrutinib treatment... The present study identified a novel prognosis risk score based on FAM associated genes and revealed the immunophenotypic differences in CLL related to FAM-Score. The function of LPL in immune response pathways demonstrates that FAM is an integral part of CLL immune regulation. Though the underlying mechanisms of fatty acid metabolic reprogramming to modulate CLL immunophenotype remain to be elucidated, FAM constitute promising targets to augment the efficacy of immunotherapy against CLL.