Brain-derived neurotrophic factor coordinates neuron-intrinsic programs to enhance axonal regeneration in human motor neurons
LMNs revealed that BDNF temporally regulated the expression and RNA stability of functionally distinct transcriptional programs that included regeneration-associated gene sets, further enhancing their expression. BDNF also regulated the phosphorylation of multiple proteins involved in cytoskeletal dynamics. In compartmentalized cultures of neurons, in which microfluidic chambers isolate somata from their axons, BDNF-induced regeneration depended on axon-specific activation of the ERK-RSK-S6K kinase pathway. The findings show that extrinsic BDNF signaling coordinates intrinsic axon-regeneration programs and highlight the role of spatially regulated kinase activation in this process.
Authors
- David Villarroel‐Campos (ORCID: https://orcid.org/0000-0003-4250-7216)
- Matteo Zanovello (ORCID: https://orcid.org/0000-0003-3343-1547)
- James N. Sleigh (ORCID: https://orcid.org/0000-0002-3782-9045)
- Jose Norberto S. Vargas (ORCID: https://orcid.org/0000-0001-5529-0883)
- Sam Bryce-Smith (ORCID: https://orcid.org/0000-0003-2087-5050)
- Anna‐Leigh Brown (ORCID: https://orcid.org/0000-0003-1493-208X)
- Andrew P. Tosolini (ORCID: https://orcid.org/0000-0001-7651-7442)
- Bethany Geary (ORCID: https://orcid.org/0000-0002-5592-5532)
- Matthew J. Keuss (ORCID: https://orcid.org/0000-0002-2628-4115)
- Giampietro Schiavo (ORCID: https://orcid.org/0000-0002-4319-8745)
- Cathleen Hagemann (ORCID: https://orcid.org/0000-0002-9900-3556)
- Andrea Serio (ORCID: https://orcid.org/0000-0002-7271-1878)
- Madeline Lombardo
- Maria Secrier (ORCID: https://orcid.org/0000-0003-2758-1741)
- Pietro Fratta (ORCID: https://orcid.org/0000-0002-8762-8188)
- Kai Sun
- Stan Majewski (ORCID: https://orcid.org/0009-0001-6423-8363)
Institutions
- Queen Mary University of London (GB)
- King's College London (GB)
- The Francis Crick Institute (GB)
- MRC Protein Phosphorylation and Ubiquitylation Unit (GB)
- UK Dementia Research Institute (GB)
- University College London (GB)
Publication Details
- Journal
- Science Signaling
- Published
- 2026-04-14
- DOI
- https://doi.org/10.1126/scisignal.adx6752
- Primary Topic
- Nerve injury and regeneration
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome Trust
- Target ALS
- Brain Research UK
- UK Research and Innovation
- Motor Neurone Disease Association
- Guarantors of Brain
- Rosetrees Trust
- UK Dementia Research Institute
- Medical Research Council