Biology subjects

Neri, C.

Publications and source records attributed to Neri, C..

4 recordsLinked to original sources

bioRxiv2025

Modeling the effects of Huntington disease on age-related genes reveals CXXC4 as an epigenetic target to restore health and excitability of Drd1-expressing striatal neurons

Neurons adapt gene expression to counter aging, yet the mechanisms by which they harness age- related genes to resist neurodegenerative disease remain elusive. We found that transcriptionalaging inversion (TAGI) in the Drd1-expressing striatal neurons (Drd1 SNs) of Huntingtons disease (HD) knock-in (Hdh) mice exhibits discrete patterns against a TAG-like (TAGL) signature. Strikingly, TAGI dynamics may explain disease progression more accurately than TAGL. Moreover, in Drd1 SNs, genes affected by 3UTR accumulation during aging are predisposed to downregulation in aging and deregulation in Hdh mice. By integrating age-related 3UTR data and Hdh-mice data, we identified a CAG-repeat-dependent network of upregulated genes with compensatory potential. This network features (i) Atad-5, a P CNA unloader that modifies CAG expansion in human HD plasma samples, and (ii) CXXC4 (IDAX), an epigenetic regulator whose early-stage upregulation is lost as behavioral symptoms worsen in Hdh mice. Functionally, CXXC4 reduces the senescence marker p16INK4a and restores glutamate excitability in human HD iPS cell-derived SNs. Collectively, these findings suggest that Drd1 SN resilience capacity against HD relies on discrete age-related patterns and responses transiently activated in early disease stages. The reactivation of specific age-related genes such as CXXC4 may notably restore cortico-striatal function in HD.

neuroscience↗

bioRxiv2025

From Lab to Industry: Awareness of the translational potential of Extracellular Vesicles by the ISEV Translation, Regulation and Advocacy Committee (ISEV-TRA).

Extracellular vesicles (EVs) are critical mediators of cellular communication, with significant potential for disease diagnosis, therapeutics, and other industrial applications. However, translating EV-based innovations into real-world products faces substantial challenges, particularly concerning regulatory frameworks and scientific gaps. To address these issues, the International Society for Extracellular Vesicles (ISEV) established the Translation, Regulation, and Advocacy Committee (ISEV-TRA) to create an environment that facilitates the translation of EV research into practical societal applications. This reporet presents the results of the first survey conducted by the ISEV-TRA, assessing the degree to which EVs have been translated into society applications, awareness of EV potential, and the current use of EVs across various industry sectors. Respondents included individuals from Academia, Industry, and dual affiliation (Academia-Industry), provided an initial perspective on EV research and its translational status. The survey highlights the growing interest in EV-based products, suggesting that there is an important wave of efforts to develop these products. Several spin-outs created by academic researchers are focusing on EV-based products, a key trend in the field, while large companies are showing increasing interest in EV-based technologies. The expectations and suggestions for the newly established ISEV-TRA underscore the need for a unified approach to accelerate the translation of EV-based technologies into practical applications. The ISEV-TRA is well-positioned to play a key role by providing essential resources, organizing workshops, and promoting interdisciplinary collaboration, ultimately driving the commercialization of EV-based innovations.

scientific communication and education↗

bioRxiv2020

Combining feature selection and shape analysis uncovers precise rules for miRNA regulation in Huntington's disease mice

BackgroundMicroRNA (miRNA) regulation is associated with several diseases, including neurodegenerative diseases. Several approaches can be used for modeling miRNA regulation. However, their precision may be limited for analyzing multidimensional data. Here, we addressed this question by integrating shape analysis and feature selection into miRAMINT, a methodology that we used for analyzing multidimensional RNA-seq and proteomic data from a knock-in mouse model (Hdh mice) of Huntingtons disease (HD), a disease caused by CAG repeat expansion in huntingtin (htt). This dataset covers 6 CAG repeat alleles and 3 age points in the striatum and cortex of Hdh mice. ResultsRemarkably, compared to previous analyzes of this multidimensional dataset, the miRAMINT approach retained only 31 explanatory striatal miRNA-mRNA pairs that are precisely associated with the shape of CAG repeat dependence over time, among which 5 pairs with a strong change of target expression levels. Several of these pairs were previously associated with neuronal homeostasis or HD pathogenesis, or both. Such miRNA-mRNA pairs were not detected in cortex. ConclusionsThese data suggest that miRNA regulation has a limited global role in HD while providing accurately-selected miRNA-target pairs to study how the brain may compute molecular responses to HD over time. These data also provide a methodological framework for researchers to explore how shape analysis can enhance multidimensional data analytics in biology and disease.

bioinformatics↗

bioRxiv2018

Loss of glutathione redox homeostasis impairs proteostasis by inhibiting autophagy-dependent protein degradation

In the presence of aggregation-prone proteins, the cytosol and endoplasmic reticulum (ER) undergo a dramatic shift in their respective redox status, with the cytosol becoming more oxidized and the ER more reducing. However, whether and how changes in the cellular redox status may affect protein aggregation is unknown. Here, we show that C. elegans mutants lacking glutathione reductase gsr-1 gene enhance the deleterious phenotypes of heterologous human as well as endogenous worm aggregation-prone proteins. These effects are phenocopied by the GSH depleting agent diethyl maleate. Additionally, gsr-1 mutants abolish the nuclear translocation of HLH-30/TFEB transcription factor, a key inducer of autophagy, and strongly impair the degradation of the autophagy substrate p62/SQST-1::GFP, revealing glutathione reductase may have a role in the clearance of protein aggregates by autophagy. Blocking autophagy in gsr-1 worms expressing aggregation-prone proteins results in strong synthetic developmental phenotypes and lethality, supporting the physiological importance of glutathione reductase in the regulation of misfolded protein clearance. Furthermore, impairing redox homeostasis in both yeast and mammalian cells induces toxicity phenotypes associated with protein aggregation. Together, our data reveal that glutathione redox homeostasis may be central to proteostasis maintenance through autophagy regulation.

genetics↗