Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases

Acta Neuropathologica Communications, Год журнала: 2025, Номер 13(1)

Опубликована: Март 5, 2025

Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer's disease, Parkinson's frontotemporal dementia (FTD) amyotrophic lateral sclerosis (ALS). A number studies have now demonstrated ER-mitochondria signaling is perturbed these there evidence this may be a driving mechanism disease onset progression. VAPB PTPIP51 tethering proteins; an ER protein outer mitochondrial membrane two proteins interact to enable inter-organelle signaling. The VAPB-PTPIP51 interaction disrupted FTD ALS. Here we review roles mechanisms by which insults disrupt interaction.

Язык: Английский

MicroRNA signature of lymphoblasts from amyotrophic lateral sclerosis patients as potential clinical biomarkers

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106871 - 106871

Опубликована: Март 1, 2025

MicroRNAs (miRNAs) are a class of small, non-coding RNAs involved in different cellular functions that have emerged as key regulators neurodegenerative diseases such amyotrophic lateral sclerosis (ALS). ALS is fatal disease lacks not only effective treatments, but also presents delays its diagnosis, since reliable clinical biomarkers unavailable. In recent years, advancements high-throughput sequencing strategies led to the identification novel biomarkers, facilitating earlier diagnosis and assessment treatment efficacy. Since immortalized lymphocytes obtained from peripheral blood suitable model study pathological features ALS, we employed these samples with aim characterize dysregulated miRNAs patients. Next-generation (NGS) was utilized order analyze expression profiles healthy controls, sporadic (sALS), familial mutations superoxide dismutase 1 (SOD1-ALS). The screening analysis NGS data identified set miRNAs, which nine candidates were selected for qRT-PCR validation, identifying first time possible importance hsa-miR-6821-5p potential biomarker. Furthermore, up-regulated predicted direct or indirect interactions genes closely related SIGMAR1, HNRNPA1 TARDBP. Additionally, by Metascape enrichment analysis, found VEGFA/VEGFR2 signaling pathway, previously implicated neuroprotective effects candidate pathway further analyses.

Язык: Английский

Empowering research in chemical biology and early drug discovery – an update from the European research infrastructure EU-OPENSCREEN

SLAS DISCOVERY, Год журнала: 2025, Номер unknown, С. 100228 - 100228

Опубликована: Апрель 1, 2025

EU-OPENSCREEN is the European research infrastructure consortium for chemical biology and early drug discovery. It provides open access to high-throughput screening, chemoproteomics spatial MS-based omics platforms medicinal chemistry groups support discovery of new biologically active small molecules that act as starting points development tool compounds drugs. Since its inauguration in 2018, evolved from a blueprint fully operational platform. As trends technologies have an important impact on modern discovery, continuously expands refines portfolio expertise. In this perspective, key achievements past six years planned activities over next are described. We illustrate how scientists can benefit through gaining technology expertise unlock extraordinary potential their projects translate them into novel, impactful innovative applications.

Язык: Английский