Urolithin A ameliorates schizophrenia-like behaviors and cognitive impairments in female rats by modulating NLRP3 signaling

International Immunopharmacology, Год журнала: 2025, Номер 151, С. 114336 - 114336

Опубликована: Фев. 22, 2025

Язык: Английский

HERV-W Env Induces Neuron Pyroptosis via the NLRP3–CASP1–GSDMD Pathway in Recent-Onset Schizophrenia

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 520 - 520

Опубликована: Янв. 9, 2025

HERVs (Human endogenous retroviruses) are remnants of ancient exogenous retroviruses that have integrated into the human genome, particularly in germ-line cells. Among these, envelope protein gene HERV-W env W family protein), located on chromosome 7 and primarily expressed placenta, has been closely linked to various neuropsychiatric disorders, including schizophrenia, as well autoimmune diseases cancer. Recent studies highlighted abnormal expression cytokines a key factor pathophysiology schizophrenia. Notably, elevated serum levels IL-1β (interleukin 1 beta) cytokine associated with inflammation, characteristic feature pyroptosis-a form pro-inflammatory programmed cell death. Although previous research observed significant upregulation pyroptosis-related genes such CASP1 (Caspase-1), NLRP3 (NLR pyrin domain containing 3), IL1B schizophrenia patients, extensive neuron pyroptosis documented Alzheimer's disease, epilepsy, multiple sclerosis, occurrence remains uncertain. Furthermore, mechanisms underlying its potential connection yet be fully elucidated. In this study, we found genes, specifically CASP1, GSDMD (Gasdermin D), IL1B, were significantly patients compared healthy controls. our analysis revealed strong positive correlation between CASP1/GSDMD/IL1B these patients. Experimental evidence further demonstrated promoted activation Caspase-1 cleavage Gasdermin D, leading increased release LDH (lactate dehydrogenase) IL-1β. Importantly, inhibitors targeting NLRP3, reduced releases induced by env, whereas BID (BH3 interacting death agonist) did not notable effect. This suggests induces CASP1-GSDMD-dependent through NLRP3-CASP1-GSDMD signaling pathway. As is increasingly recognized for neurodegenerative diseases, study provides insights molecular neuronal mediated inflammasome context env. Additionally, it explores facilitation development via pyroptosis, proposing certain indicators could serve biomarkers Based existing results findings researchers, infer acts bridge onset progression may target clinical treatment suggesting monoclonal antibody therapy represent novel approach managing disease.

Язык: Английский

Unraveling the potential of neuroinflammation and autophagy in schizophrenia

European Journal of Pharmacology, Год журнала: 2025, Номер 997, С. 177469 - 177469

Опубликована: Март 5, 2025

Язык: Английский