bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2025–08–24
fifteen papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. Using plasma cell-free mRNA to profile immune response and myocardial damage in immune checkpoint inhibitor-induced myocarditis.
  2. Fluorescent GLP1R/GIPR dual agonist probes reveal cell targets in the pancreas and brain.
  3. O-GlcNAc transferase plays dual antiviral roles by integrating innate immunity and lipid metabolism.
  4. Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment.
  5. Lighting up targets of dual agonist therapies for diabetes and obesity.
  6. RNA Pol II inhibition activates cell death independently from the loss of transcription.
  7. 'Computing is a Black people's thing'.
  8. Metabolic Messenger: growth differentiation factor 15.
  9. A single-cell, spatial transcriptomic atlas of the Arabidopsis life cycle.
  10. Why nurturing the gut microbiota could resolve depression and anxiety.
  11. Antibiotics unleash neuroinflammation.
  12. People are having fewer babies: Is it really the end of the world?
  13. Alpha-synuclein interacts with regulators of ATP homeostasis in mitochondria.
  14. Hypertension promotes bone loss and fragility by favoring bone resorption in mouse models.
  15. Modulators of the stress response.
  1. J Clin Invest. 2025 Aug 15. pii: e188817. [Epub ahead of print]135(16):
    Using plasma cell-free mRNA to profile immune response and myocardial damage in immune checkpoint inhibitor-induced myocarditis.
    Alireza Raissadati, Xuanyu Zhou, Harrison Chou, Yuhsin Vivian Huang, Shaheen Khatua, Yin Sun, Anne Xu, Sharon Loa, Arturo Hernandez, Han Zhu, Sean M Wu.
      Plasma cell-free mRNA provides tissue-specific transcriptional profiling, precisely capturing cardiac damage and immune responses in immunotherapy-induced myocarditis.
    Keywords:  Autoimmune diseases; Cardiology; Diagnostics; Immunology; Molecular diagnosis
    DOI:  https://doi.org/10.1172/JCI188817
  2. Nat Metab. 2025 Aug;7(8): 1536-1549
    Fluorescent GLP1R/GIPR dual agonist probes reveal cell targets in the pancreas and brain.
    Anne de Bray, Anna G Roberts, Sarah Armour, Jason Tong, Christiane Huhn, Blaise Gatin-Fraudet, Kilian Roßmann, Ali H Shilleh, Wanqing Jiang, Natalie S Figueredo Burgos, James P P Trott, Katrina Viloria, Daniela Nasteska, Abigail Pearce, Satsuki Miyazaki, Jeremy W Tomlinson, Dylan M Owen, Daniel J Nieves, Julia Ast, Malgorzata Cyranka, Alexey Epanchintsev, Carina Ämmälä, Frank Reimann, Tolga Soykan, Graham Ladds, Alice E Adriaenssens, Stefan Trapp, Ben Jones, Johannes Broichhagen, David J Hodson.
      Dual agonists targeting glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are breakthrough treatments for patients with type 2 diabetes and obesity. Compared to GLP1R agonists, dual agonists show superior efficacy for glucose lowering and weight reduction. However, delineation of dual agonist cell targets remains challenging. Here, we develop and test daLUXendin and daLUXendin+, non-lipidated and lipidated fluorescent GLP1R/GIPR dual agonist probes, and use them to visualize cellular targets. daLUXendins are potent GLP1R/GIPR dual agonists that advantageously show less functional selectivity for mouse GLP1R over mouse GIPR. daLUXendins label rodent and human pancreatic islet cells, with a signal intensity of β cells > α cells = δ cells. Systemic administration of daLUXendin strongly labels GLP1R+ and GIPR+ neurons in circumventricular organs characterized by an incomplete blood-brain barrier but does not penetrate the brain beyond labelling seen with single (ant)agonists. At the single-molecule level, daLUXendin targets endogenous GLP1R-GIPR nanodomains, which differ in organization and composition from those targeted by a single agonist. daLUXendins reveal dual agonist targets in the pancreas and brain and exclude a role for brain penetration in determining the superior efficacy of dual agonists, shedding new light on different modes of action of dual agonists versus single agonists.
    DOI:  https://doi.org/10.1038/s42255-025-01342-6
  3. Nat Commun. 2025 Aug 19. 16(1): 7721
    O-GlcNAc transferase plays dual antiviral roles by integrating innate immunity and lipid metabolism.
    Hong Dong, Chenxi Liang, Junjie Zhang, Weidong Wu, Nitesh Kumar, Zihao Liu, Yajun Sun, Zhiwei Liao, Xiaolin Cheng, Yanbao Yu, Yong Zhang, Michael J Holtzman, Jianrong Li, Kymberly M Gowdy, Paul G Thomas, Jovica D Badjic, Anjun Ma, Qin Ma, Jacob S Yount, Shan-Lu Liu, Haitao Wen.
      Viral infection induces robust reprogramming of metabolic pathways in host cells. However, whether host metabolic enzymes detect viral components remains unknown. Our group and others previously identified O-GlcNAc transferase (OGT), an important glucose metabolic enzyme, as a crucial mediator of the antiviral immune responses. Here, by studying a mouse model with a catalytically impaired OGT, we discover a catalytic activity-independent function of OGT in restraining influenza A virus (IAV) infection in addition to its catalytic activity-dependent effect on MAVS-mediated antiviral immunity. Biochemical studies reveal a critical antiviral effect based on OGT interacting with IAV genomic RNA that requires its N-terminal tetracopeptide repeat-4 motif. This interaction causes the translocation of nuclear OGT to cytosolic lipid droplets (LDs) to destabilize LDs-coating perilipin 2, thereby limiting LDs accumulation and in turn virus replication. In sum, our findings reveal OGT as a multifaceted metabolic sensor that integrates MAVS signaling and lipid metabolism to combat viral infection.
    DOI:  https://doi.org/10.1038/s41467-025-63085-y
  4. Nat Aging. 2025 Aug 19.
    Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment.
    Laura Remesal, Juliana Sucharov-Costa, Yuting Wu, Karishma J B Pratt, Gregor Bieri, Amber Philp, Mason Phan, Turan Aghayev, Charles W White, Elizabeth G Wheatley, Bende Zou, Brandon R Desousa, Julien Couthouis, Isha H Jian, Xinmin S Xie, Yi Lu, Jason C Maynard, Alma L Burlingame, Saul A Villeda.
      Understanding cellular and molecular drivers of age-related cognitive decline is necessary to identify targets to restore cognition at old age. Here we identify ferritin light chain 1 (FTL1), an iron-associated protein, as a pro-aging neuronal factor that impairs cognition. Using transcriptomic and mass spectrometry approaches, we detect an increase in neuronal FTL1 in the hippocampus of aged mice, the levels of which correlate with cognitive decline. Mimicking an age-related increase in neuronal FTL1 in young mice alters labile iron oxidation states and promotes synaptic and cognitive features of hippocampal aging. Targeting neuronal FTL1 in the hippocampi of aged mice improves synaptic-related molecular changes and cognitive impairments. Using neuronal nuclei RNA sequencing, we detect changes in metabolic processes, such as ATP synthesis, and boosting these metabolic functions through NADH supplementation mitigated pro-aging effects of neuronal FTL1 on cognition. Our data identify neuronal FTL1 as a key molecular mediator of cognitive rejuvenation.
    DOI:  https://doi.org/10.1038/s43587-025-00940-z
  5. Nat Metab. 2025 Aug;7(8): 1507-1508
    Lighting up targets of dual agonist therapies for diabetes and obesity.
      
    DOI:  https://doi.org/10.1038/s42255-025-01346-2
  6. Cell. 2025 Aug 14. pii: S0092-8674(25)00856-6. [Epub ahead of print]
    RNA Pol II inhibition activates cell death independently from the loss of transcription.
    Nicholas W Harper, Gavin A Birdsall, Megan E Honeywell, Kelly M Ward, Athma A Pai, Michael J Lee.
      RNA Pol II-mediated transcription is essential for eukaryotic life. Although loss of transcription is thought to be universally lethal, the associated mechanisms promoting cell death are not yet known. Here, we show that death following the loss of RNA Pol II activity does not result from dysregulated gene expression. Instead, it occurs in response to loss of the hypophosphorylated form of Rbp1 (also called RNA Pol IIA). Loss of RNA Pol IIA exclusively activates apoptosis, and expression of a transcriptionally inactive version of Rpb1 rescues cell viability. Using functional genomics, we identify the mechanisms driving lethality following the loss of RNA Pol IIA, which we call the Pol II degradation-dependent apoptotic response (PDAR). Using the genetic dependencies of PDAR, we identify clinically used drugs that owe their lethality to a PDAR-dependent mechanism. Our findings unveil an apoptotic signaling response that contributes to the efficacy of a wide array of anti-cancer therapies.
    Keywords:  BCL2L12; DNA damage; PTBP1; RNA polymerase II; apoptosis; cancer therapy; cell death; chemotherapy; cisplatin; transcription
    DOI:  https://doi.org/10.1016/j.cell.2025.07.034
  7. Nature. 2025 Aug 18.
    'Computing is a Black people's thing'.
    Meghie Rodrigues.
      
    Keywords:  Careers; Physics; Scientific community; Society
    DOI:  https://doi.org/10.1038/d41586-025-02298-z
  8. Nat Metab. 2025 Aug 18.
    Metabolic Messenger: growth differentiation factor 15.
    Samuel N Breit, Vicky W Tsai.
      Growth differentiation factor 15 (GDF15; also known as macrophage-inhibitory cytokine-1) is a stress-responsive cytokine that is overexpressed under a broad range of conditions. It has a role in regulating appetite and body weight and is an aetiological factor in anorexia-cachexia syndromes, as well as nausea and vomiting during pregnancy. Long after its original cloning, its receptor was identified as GFRAL, a distant member of the GDNF receptor family within the TGFβ superfamily, with RET as its co-receptor. Both of these are highly localized to specific hindbrain regions. Although many of GFRAL's metabolic changes may be linked to its effect on suppressing appetite, recent findings suggest that GDF15 also independently regulates energy expenditure and insulin sensitivity. Here, we review recent literature and provide updates on the current understanding of GDF15 biology and its therapeutic applications in health and metabolic diseases.
    DOI:  https://doi.org/10.1038/s42255-025-01353-3
  9. Nat Plants. 2025 Aug 19.
    A single-cell, spatial transcriptomic atlas of the Arabidopsis life cycle.
    Travis A Lee, Natanella Illouz-Eliaz, Tatsuya Nobori, Jiaying Xu, Bruce Jow, Joseph R Nery, Joseph R Ecker.
      Arabidopsis has been pivotal in uncovering fundamental principles of plant biology, yet a comprehensive, high-resolution understanding of its cellular identities throughout the entire life cycle remains incomplete. Here we present a single-nucleus and spatial transcriptomic atlas spanning ten developmental stages, encompassing over 400,000 nuclei from all organ systems and tissues-from seeds to developing siliques. Leveraging paired single-nucleus and spatial transcriptomic datasets, we annotate 75% of identified cell clusters, revealing striking molecular diversity in cell types and states across development. Our integrated approach identified conserved transcriptional signatures among recurrent cell types, organ-specific heterogeneity and previously uncharacterized cell-type-specific markers validated spatially. Moreover, we uncover dynamic transcriptional programs governing secondary metabolite production and differential growth patterns, exemplified by detailed spatial profiling of the compact yet complex apical hook structure; this profiling revealed transient cellular states linked to developmental progression and hormonal regulation, highlighting the hidden complexity underlying plant morphogenesis. Functional validation of genes uniquely expressed within specific cell contexts confirmed their essential developmental roles, underscoring the predictive power of our atlas. Collectively, this comprehensive resource provides an invaluable foundation for exploring cellular differentiation, environmental responses and genetic perturbations at high resolution, advancing our understanding of plant biology.
    DOI:  https://doi.org/10.1038/s41477-025-02072-z
  10. Nature. 2025 Aug 18.
    Why nurturing the gut microbiota could resolve depression and anxiety.
    Simon Makin.
      
    Keywords:  Depression; Microbiome; Psychiatric disorders
    DOI:  https://doi.org/10.1038/d41586-025-02633-4
  11. J Exp Med. 2025 Sep 01. pii: e20251233. [Epub ahead of print]222(9):
    Antibiotics unleash neuroinflammation.
    Jessica E Kenison, Francisco J Quintana.
      The gut microbiome limits neuroinflammation and neurocognitive decline in acute graft-versus-host disease by modulating microglial activation via a mechanism mediated by the microbial metabolite TMAVA (Chatterjee et al. https://doi.org/10.1084/jem.20242180).
    DOI:  https://doi.org/10.1084/jem.20251233
  12. Nature. 2025 Aug;644(8077): 594-596
    People are having fewer babies: Is it really the end of the world?
    Lynne Peeples.
      
    Keywords:  Geography; Human behaviour; Policy; Society
    DOI:  https://doi.org/10.1038/d41586-025-02615-6
  13. Nat Commun. 2025 Aug 16. 16(1): 7651
    Alpha-synuclein interacts with regulators of ATP homeostasis in mitochondria.
    Tetiana Serdiuk, Yanick Fleischmann, Dhiman Ghosh, Aro Delparente, Viviane Reber, Larissa Frey, David Rhyner, Juan Gerez, Norbert Volkmar, Lucie Kralickova, Guillaume Mas, Christian Dörig, Sebastian Hiller, Roger Schibli, Linjing Mu, Paola Picotti, Roland Riek.
      Mitochondrial dysfunction and accumulation of α-synuclein aggregates are hallmarks of the neurodegenerative Parkinson's disease and may be interconnected. To investigate the interplay between α-synuclein and brain mitochondria at near atomic structural level, we apply NMR and identify α-synuclein protein interactors using limited proteolysis-coupled mass spectrometry (LiP-MS). Several of the proteins identified are related to ATP synthesis and homeostasis and include subunits of ATP synthase and the adenylate kinase AK2. Furthermore, our data suggest that α-synuclein interacts with the Parkinson's disease-related protein DJ1. NMR analysis demonstrates that both AK2 and DJ1 bind to the C-terminus and other segments of α-synuclein. Using a functional assay for AK2, we show that monomeric α-synuclein has an activating effect, whereas C-terminally truncated α-synuclein and α-synuclein in an amyloid fibrillar state have no significant effect on AK2 activity. Our results suggest that α-synuclein modulates ATP homeostasis in a manner dependent on its conformation and its C-terminal acidic segment.
    DOI:  https://doi.org/10.1038/s41467-025-62895-4
  14. J Clin Invest. 2025 Aug 19. pii: e184325. [Epub ahead of print]
    Hypertension promotes bone loss and fragility by favoring bone resorption in mouse models.
    Elizabeth M Hennen, Sasidhar Uppuganti, Néstor de la Visitación, Wei Chen, Jaya Krishnan, Lawrence A Vecchi Iii, David M Patrick, Mateusz Siedlinski, Matteo Lemoli, Rachel Delgado, Mark P de Caestecker, Wenhan Chang, Tomasz J Guzik, Rachelle W Johnson, David G Harrison, Jeffry S Nyman.
      Inflammatory diseases contribute to secondary osteoporosis. Hypertension is a highly prevalent inflammatory condition that is clinically associated with reduced bone mineral density and increased risk for fragility fracture. In this study, we showed that a significant loss in bone mass and strength occurs in two pre-clinical models of hypertension. This accompanied increases in immune cell populations, including monocytes, macrophages, and IL-17A-producing T cell subtypes in the bone marrow of hypertensive mice. Neutralizing IL-17A in angiotensin (ang) II-infused mice blunted hypertension-induced loss of bone mass and strength due to decreased osteoclastogenesis. Likewise, the inhibition of the CSF-1 receptor blunted loss of bone mass and prevented loss of bone strength in hypertensive mice. In an analysis of UK Biobank data, circulating bone remodeling markers exhibited striking associations with blood pressure and bone mineral density in > 27,000 humans. These findings illustrate a potential mechanism by which hypertension activates immune cells in the bone marrow, encouraging osteoclastogenesis and eventual loss in bone mass and strength.
    Keywords:  Bone biology; Bone disease; Bone marrow; Hypertension; Immunology; Inflammation
    DOI:  https://doi.org/10.1172/JCI184325
  15. Nat Chem Biol. 2025 Aug 19.
    Modulators of the stress response.
    Yiyun Song.
      
    DOI:  https://doi.org/10.1038/s41589-025-02014-y
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