CAPN2 (Calpain 2)

Rather, its overexpression in spinal CaMKII neurons directly promotes nociceptive signaling, most likely through disruption of plasma membrane calcium dynamics. Collectively, the results identify CAPN1 as a candidate therapeutic target for the clinical treatment and prevention of PINP.

The high expression of LAD1 in cancer cells, its associations with LUAD-related genes, and its links to biological processes and pathways suggest its potential biological relevance and that it merits further investigation. Overall, this study provides insights into LUAD and supports LAD1 as a gene worthy of further investigation.

Therefore, this article discusses the expression and function of calpain-1 and calpain-2 (ubiquitous calpains) in various innate (epithelial, endothelial, dendritic, mast, and NK cells, as well as macrophages) and adaptive (T and B cells) immune cells, affecting inflammation and immune regulation. As inflammatory diseases are on the rise due to several factors, such as environment, lifestyle, and an aging population, we must not just investigate but strive for a deeper understanding of the inflammation and immunoregulation under the calpain system (calpain-1 and calpain-2 and their endogenous negative regulator calpastatin) lens, which is ubiquitous and senses cytosolic Ca2+ changes to impact immune response.

These persistent molecular differences suggest spontaneous weaning as the optimal model for healthy mammary gland regression, whereas forced weaning sustains alterations in calpain-2 and regulatory miRs that may increase post-partum breast cancer risk. The potential long-term influence of lactation duration on breast cancer development warrants further consideration in both clinical and public health contexts.

These effects were mediated by multiple molecular mechanisms, including impaired actin filament remodeling due to calpain-2 deficiency, reduced activation of Matrix Metalloproteinase (MMP)-2 and MMP-9, and decreased expression of EMT-related transcription factors such as Snail, Slug, and ZEB1. Collectively, these findings suggest that calpain-2 plays a central role in TGF-β-mediated cancer cell migration, invasion, and EMT progression, and that targeting calpain-2 function may represent a potential therapeutic strategy for inhibiting lung cancer metastasis.

BC types were differentiated based on calpain-2 and cystatin-C expression (p < 0.05). Thus, BC has distinct urinary-protein profiles based on clinical diagnosis, which could be used in real-time noninvasive BC monitoring.

These findings indicate that CAPN-1 and CAPN-2 may exert antagonistic roles in breast cancer, but importantly, this effect was restricted to HCC1937 cells, representing a basal A TNBC subtype. Validation in additional basal A models and patient-derived samples will be essential to confirm these results. Our study, therefore, provides preliminary, model-specific insights into calpain regulation in TNBC and suggests that future therapeutic strategies should carefully account for subtype heterogeneity.

We hypothesize that coronin 1 downregulation contributes to the transition from undifferentiated to differentiated glioblastoma cells, supporting invasion and EMT-like phenotype. Further investigation of coronin 1's role in glioblastoma could offer novel therapeutic strategies for targeting tumor aggressiveness.

However, this peptide inhibitor was not effective in vivo at reducing metastasis under the conditions used (vehicle vs. CAST, 1.12 ± 1.35 lung metastases per mm2 vs. 0.34 ± 0.20 metastases per mm2), likely due to rapid clearance, as indicated by the short serum half-life. This work demonstrates that calpain-1/2 disruption effectively abrogates metastasis and provides rationale for development of effective calpain inhibitors.

In conclusion, this study provides strong evidence that lapatinib or pazopanib significantly improved motor function, alleviated cognitive decline, and attenuated neurodegeneration in HD rats via modulating key signalling pathways implicated in HD pathogenesis. These results underscore the promising therapeutic potential of TKIs in managing HD and warrant further investigation into their clinical application.

By using an internal isotope-labeled standardization approach, our present strategy enables direct and accurate quantification of CAPN2 activity using PS-MS platform, without external procurement. This strategy holds great promise for other types of protease detection systems by substituting the protease-specific peptide substrates.

Future research should aim to validate these findings using larger, balanced cohorts and include longitudinal CSF and serum analysis. Experimental in vitro or in vivo studies investigating CAPN1 inhibition and its impact on HMGB1-related signalling are necessary to explore therapeutic implications.