CAV3 (Caveolin 3)

Our review aims to elaborate the impact of CAV on diverse stem cell populations and regulatory mechanisms, as well as point out novel insights brought by CAV and stem cell therapy in the management of CDD, such as stroke, Alzheimer's disease (AD), Parkinson's disease (PD), diabetes, pulmonary arterial hypertension (PAH), breast cancer and liver cancer. Based on scientometrics studies, this review synthesizes current analyses of the CAV family's role in determining the fate of various stem cell populations, thereby providing new perspectives for the prevention and treatment of CDD.

Compounds 1-4 showed no significant inhibitory activity on hERG (Human Ether-à-go-go-related gene) and CaV3.1 (T-type calcium) channels. Additionally, all isolates showed no significant cytotoxicity against Hela, HCT8 and MCF7 human cancer cells in vitro.

After levothyroxine adjustment, repeat TSH was normal and repeat CK was 306 U/L...Carbunar has received research support from National Institute of Arthritis and Musculoskeletal and Skin Diseases. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.

These findings demonstrate a critical role for T-type calcium channels, particularly CaV3.3, in mediating chemoresistance in retinoblastoma. Our results suggest that targeting these channels may provide a potential strategy to enhance the efficacy of carboplatin-based therapy in retinoblastoma treatment.

To lay the groundwork for the future rational optimization of this promising class of compounds, the molecular bases of DM1 and DM2 activity were investigated by modelling their interaction with hCav3.1 channels. The calculated binding modes of DM1 and DM2 to hCav3.1 channels partially mirrored that of the selective Cav3.1 blocker Z944, paving the way for future lead optimization.

The Cav3 blocker drug mibefradil synergized with temozolomide (TMZ) and radiation to reduce in vivo tumor growth and prolong animal survival. Conclusions Together these data reveal a role for microenvironment Cav3 in promoting GBM tumor progression through regulating neuronal and glial processes particularly associated with the OPC-cell state. Targeting both intrinsic and microenvironment Cav3 with the inhibitor mibefradil significantly enhanced the anti-GBM effects of TMZ and radiation.

In addition, Cav3.2 KO also attenuated hepatic lipid accumulation, oxidative stress, inflammation and hepatocyte apoptosis in palmitic acid/oleic acid (PAOA)-treated primary hepatocytes. These results suggest that therapeutic approaches targeting Cav3.2 provide effective approaches for treating NAFLD.

Gossypol differentially blocked CaV3 channel and its anticancer activity was correlated with high levels of CaV3.1 and CaV3.2 in colorectal cancer cells. The CaV3 regulates cell proliferation and Ca2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies.

Expression of rCacna1h in PC12 cells induced differential protein expression profiles determined by mass spectrometry as well as a shift in the membrane potential where maximum calcium currents were observed as determined by electrophysiology. The findings suggest the involvement of CACNA1H/CaV3.2 in pheochromocytoma development and establish a potential link between the aetiology of adrenomedullary and adrenocortical tumor development.

As both CaV3.2 and CaV3.3 have been implicated in peripheral pain signaling, the analgesic potential of Hf1a-NH2 was explored in vivo in a mouse model of incision-induced acute post-surgical pain. Consistent with this role, Hf1a-NH2 produced antiallodynia in both mechanical and thermal pain.

In mice with inflammation, mechanical hypersensitivity was suppressed by blockers of both channels. These data suggest that the interaction of Cav3.2 with TRPA1 in sensory neurons is enhanced via the augmentation of the activities of both channels under inflammatory conditions, indicating that both channels are therapeutic targets for inflammatory pain.

Despite the clinical trials of TTCC blockers like Z944 and MK8998, none are currently available on the market. The most potent derivative, compound 7, exhibited an IC50 value of 0.19 ± 0.03 μM and was further analyzed through molecular docking, revealing key interactions with Cav3.1. These findings provide a foundation for the structural optimization of Cav3.1 calcium channel blockers and present compound 7 as a promising lead compound for drug development and a tool for chemical biology research.