Open access

Neuronal expression of bromodomain proteins alters neuronal health and peripheral protein homeostasis to promote longevity

Naibedya Dutta Daniel Hicks Edgar Esparza Anna Entin Priyadharshini Vijayakumar Caitlin M. Lange Tripti Nair Elijah A. Roditi Athena Alcala Maxim Averbukh Matthew Vega Rebecca Aviles Barahona Caitlin McTygue Veronica Kuo Juri Kim Herbert Anson A. Coakley George Wang Steven E. Pilley Max A. Thorwald Whitaker Cohn Sean P. Curran N. Brouilly Caroline Kumsta Rachel N. Arey Peter J. Mullen Gilberto Garcia Ryo Higuchi-Sanabria

Aug 2026 · Genes & Development · Vol 40, pp. 1523 - 1552 · 0 citations · 141 references

Medicine

TL;DR

It is shown that the neuronal expression of the chromatin reader BET-1 promotes longevity and resilience in C. elegans through signaling mechanisms involving master transcription factors HSF-1 and DAF-16 and neurotransmitter UNC-13.

Abstract

In this study, Dutta et al. show that the neuronal expression of the chromatin reader BET-1 promotes longevity and resilience in C. elegans. Neuronal BET-1 activates various prolongevity transcriptional programs—including proteostasis, immune response to pathogens, and metabolism—through signaling mechanisms involving master transcription factors HSF-1 and DAF-16 and neurotransmitter UNC-13.

DOI PubMed Semantic Scholar

Read PDF

Similar papers

Aug 2026

Wiring autophagy: Neural circuits regulate lysosomal homeostasis in muscle.

Autophagy is commonly viewed as a cell-autonomous degradative process governed by intracellular metabolic and stress signals,1 but how autophagy is coordinated across tissues in multicellular organisms remains unclear. Zheng et al. 2 identify two parallel neuronal circuits that non-cell-autonomously regulate muscle autophagy in C. elegans, revealing an unexpected role for the nervous system in orchestrating peripheral autophagy.

Min Chen, Congcong He · Developmental Cell · 0 citations

Open access Mar 2025

Dual regulation of the unfolded protein response by IGF2BP3 during ER stress

Misfolded protein accumulation in the endoplasmic reticulum (ER) perturbs cellular homeostasis, causing pathological ER stress. The Unfolded Protein Response (UPR) is a highly conserved signaling cascade that restores ER homeostasis by countering ER protein overload. Transcriptional response is paramount for UPR signaling and negating ER stress. While multiple UPR-linked mRNAs are post-transcriptionally regulated, the mechanisms mediating this regulation are unclear. Here, we demonstrate that the highly conserved RNA-binding protein IGF2BP3 interacts with transcripts encoding a subset of UPR effectors. During ER stress, IGF2BP3 destabilized many of these target transcripts, including UPR targets. In contrast, IGF2BP3 stabilized mRNAs encoding transcriptional regulators and thereby upregulated expression of UPR target genes. This dual regulation allows IGF2BP3 to differentially upregulate stress response genes while tuning down the expression of other transcripts during ER stress, relieving protein folding load during this critical response. Our data reveal that posttranscriptional mechanisms control transcription, thus forming gene regulatory networks that robustly tune the UPR.

A. Anisimova, Sabina Omerbegovic, Milica Mihailovic et al. · bioRxiv · 0 citations

Open access Jul 2026

Inhibition of leucine‐rich kinase 2 (LRRK2) promotes peripheral axon regeneration via phosphorylation‐network remodelling

In contrast to neurons in the central nervous system, neurons in the peripheral nervous system can regenerate axons after injury via activation of a pro‐regenerative transcriptional programme. Pathogenic mutations in leucine‐rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease, and several small‐molecule LRRK2 kinase inhibitors have been developed, with some in clinical trials. However, the physiological role of endogenous, non‐pathogenic LRRK2 remains largely unknown.

Eun-Hae Jang, E. Yang, Gil Song et al. · British Journal of Pharmacol... · 0 citations

Aug 2026

Protein restriction and the hallmarks of aging: A coordinated physiological adaptive response?

Protein restriction extends lifespan across species and engages many hallmarks of aging. We propose that these diverse responses can be understood as components of a single coordinated physiological state. This response involves both cellular nutrient sensing and endocrine and neural coordination, with enhanced longevity emerging from this adaptive response.

Sora Q. Kim, Sang-Ho Yu, C. Morrison · Cell Metabolism · 0 citations

Aug 2026

Allosteric rewiring of mitochondrial stress signaling through Miro1.

In this issue of Cell Chemical Biology, Chandra and colleagues1 demonstrate that allosteric modulation of the mitochondrial protein Miro1 can selectively reprogram mitochondrial stress signaling. Chemical targeting of a single molecular hub can produce distinct responses in disease-relevant cell types, despite acting within a broadly conserved stress pathway.

Layla Drwesh, Julia C Fitzgerald · Cell Chemical Biology · 0 citations

Aug 2026

The miRNA Argonaute protein, ALG-2, maintains neurobehaviors in adult C. elegans

microRNAs (miRNAs) are short, non-coding RNAs essential for gene regulation in many different processes, including neuronal development. However, the role of the miRNA pathway in maintaining neuronal health throughout aging is less understood. Here, we ask how the miRNA pathway in adulthood impacts neurobehaviors in C. elegans . Argonaute-like Gene 2 ( ALG-2 ) is a protein required for the accumulation and function of certain miRNAs in C. elegans . Using the auxin-inducible degron 2 (AID2) system for temporal knockdown, we demonstrate that the miRNA Argonaute protein, ALG-2 , is required throughout adulthood to maintain two well-characterized neurobehaviors, basal slowing response and mechanosensation.

Ava Chon, Run-Tian Jiang, Yuxuan Guo et al. · microPublication Biology · 0 citations