Biology subjects

Chhipa, S.

Publications and source records attributed to Chhipa, S..

3 recordsLinked to original sources

bioRxiv2026

Genetic and structural interpretation of NLRP1 FIIND domain variants in glioma in an Indian cohort: a pilot study

Gliomas, particularly glioblastoma (GBM), are aggressive primary brain tumors associated with dysregulated NLR signaling, a pathway central to innate immunity and inflammation. NLRP1 triggers proinflammatory cytokine release and pyroptotic cell death via autoproteolytic cleavage. The FIIND missense variant rs11651270 (M1184V) may modulate this cleavage process. While NLRP1 polymorphisms are associated with various diseases and cancers, their specific impact on glioma remains to be investigated. In our study, five FIIND-domain single-nucleotide polymorphisms (SNPs) of NLRP1 rs371579423, rs58604457, rs57636751, rs11651270, and rs2301583, were investigated by Sanger sequencing in a clinical cohort of glioma patients and compared against population-matched controls from the GenomeIndia dataset (Rajasthan cohort) using genetic association models. Molecular dynamics simulations were performed to evaluate the structural effects of the missense variant rs11651270 (M1184V) in NLRP1 during pre- and post-cleavage states. The linked variants rs58604457 (G>A) and rs57636751 (C>T) exhibited complete linkage disequilibrium (r2=1.00) and were significantly associated with lower odds of glioma (odds ratio ~0.5). The missense variant rs11651270 (T>C) showed no association with glioma risk. Notably, the SNP rs2301583 had a higher allelic frequency in glioma cases despite being absent in the GenomeIndia population-based control catalogue. Molecular dynamics simulations revealed that the M1184V substitution stabilizes local FIIND architecture by preserving {beta}-strand organization through persistent interactions with neighboring residues. This study provides the first combined genetic and structural analysis of NLRP1 FIIND-domain variants in an Indian glioma cohort. These findings illustrate the potential value of integrating population-based genetic association with structural modelling to generate hypotheses and uncover potential functional mechanisms of inflammasome-gene variants in neuro-oncology.

cancer biology↗

bioRxiv2025

Repurposing Nelfinavir: AIM2 Inflammasome-Driven Anti-tumor Effects in Glioblastoma

Nelfinavir (NFR), originally developed as an antiretroviral agent for the human immunodeficiency virus, has demonstrated anti-cancer properties across various malignancies; however, its therapeutic potential in Glioblastoma (GBM) remains largely unexplored. In the present study, we investigated the anti-tumor effects of NFR in GBM using a comprehensive panel of experimental models, including established GBM cell lines, GBM cell line-derived spheroids, patient-derived primary glioma cells, and patient-derived glioma organoids. We further evaluated the synergistic potential of NFR in combination with standard chemotherapeutic agents, Carboplatin and Doxorubicin, across these platforms. In vitro analyses revealed that NFR significantly inhibits GBM cell proliferation and induces both apoptotic and necrotic cell death. Mechanistically, we identified activation of the AIM2 inflammasome as a potential additional pathway mediating the anti-tumor effects of NFR. Collectively, our findings highlight NFR as a promising therapeutic candidate for GBM, exerting its effects through anti-proliferative and pro-death mechanisms potentially linked to AIM2 inflammasome activation.

cancer biology↗

bioRxiv2024

Innate Immune Receptor NLRX1: Potential Modulator of Glioblastoma Pathophysiology

Gliomas are primary brain tumors that develop from glial cells within the central nervous system and are among the deadliest human cancers. Glioblastoma (GBM) is the most malignant form of glioma. NLRX1 is an innate immune pattern recognition receptor that exhibits tumor-suppressive and tumor-promoting effects that may be cancer or cell-type, context-dependent, aided by differences in the microenvironment. Here, we report that NLRX1 is differentially expressed in microglia, astrocytes, GBM cell lines, and glioma patient tissues. siRNA-mediated silencing of Nlrx1 decreases the ability of the GBM cell line, LN-229, to proliferate and migrate. Nlrx1-/- GBM cells exhibit attenuated ability to generate 3D spheroids and enhanced capability to form tunneling nanotubes. Moreover, Nlrx1-/- GBM cells show decreased expression of autophagy markers, suggesting that NLRX1 plays a role in maintaining autophagy in GBM. In summary, our findings indicate that NLRX1 may modulate GBM pathophysiology by regulating GBM cell proliferation, migration, and metabolism. We believe our understanding of NLRX1 in GBM pathophysiology paves the potential development of GBM-targeting therapeutics that may delay disease progression and/or improve survival.

cancer biology↗