Connectivity mapping: Integrating omics data, drug targets, and disease drivers for drug discovery and repurposing

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Case Report: De novo variant of the NUS1 gene associated with developmental delay and autism spectrum disorders in a Chinese family

Frontiers in Pediatrics, Год журнала: 2025, Номер 13

Опубликована: Май 14, 2025

Nuclear undecaprenyl pyrophosphate synthase 1 (NUS1) has been implicated in the pathogenesis of neurodevelopmental disorders, including Parkinson's disease, seizures, intellectual disability, dystonia, and congenital disorder glycosylation. To this day, there have limited studies reports on NUS1 gene. We described case an 8-year-old Chinese boy exhibiting developmental delay, autism spectrum (ASD). elucidate genetic etiology, whole-exome sequencing was performed proband. A candidate variant subsequently validated by Sanger proband his unaffected parents. Whole-exome analysis discovered a novel heterozygous (c.279del, p.L94Wfs*11) exon (NM_138459.5), leading to premature termination protein translation (p.L94Wfs*11). failed identify Following updated American College Medical Genetics Genomics guidelines, c.279del classified as pathogenic (PVS1+PM6+PM2_Supporting). Based clinical phenotype proband, he diagnosed with autosomal dominant disorder-55 seizures (MRD55) ASD. This study expands mutation gene, which contributes diagnosis related disorders. Furthermore, identification basis confirmation corresponding loci family members will facilitate counseling proband's parents regarding reproduction.

Язык: Английский

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PU-H71 (NSC 750424): a molecular masterpiece that targets HSP90 in cancer and beyond

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 5, 2024

Heat shock protein 90 (HSP90) is a pivotal molecular chaperone with multifaceted roles in cellular health and disease. Herein, we explore how HSP90 orchestrates stress responses, particularly through its partnership heat factor 1 (HSF-1). PU-H71, selective inhibitor of HSP90, demonstrates significant potential cancer therapy by targeting wide array oncogenic pathways. By inducing the degradation multiple client proteins, PU-H71 disrupts critical signaling pathways such as MAPK, PI3K/Akt, JAK/STAT, EGFR, mTOR, which are essential for cell survival, proliferation, metastasis. We examined impact on combating triple-negative breast enhancing effectiveness carbon-ion beam therapy, offering new avenues treatment. Furthermore, dual inhibition HSP90A HSP90B1 proves highly effective context myeloma, providing fresh hope patients this challenging malignancy. delve into to induce apoptosis B-cell lymphomas that rely Bcl6 highlighting relevance realm hematologic cancers. Shifting our focus hepatocellular carcinoma, innovative approaches chemotherapy. Moreover, current review elucidates capacity suppress glial activation paving way developing novel therapeutic strategies neuroinflammatory disorders. Additionally, present report also suggests promising role JAK2-dependent myeloproliferative neoplasms. Eventually, sheds more light functions well benefit an diseases, laying foundations development could achieve better treatment outcomes.

Язык: Английский

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Editorial overview: Protein networks in health and disease

Current Opinion in Structural Biology, Год журнала: 2024, Номер 90, С. 102953 - 102953

Опубликована: Дек. 5, 2024

Язык: Английский

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