Growth factors control biological processes by binding to receptors and activating cellular mechanisms such as survival and growth. Glial Cell Line-Derived Growth Factor (GDNF) is associated with improving survival of neurons in neurodegenerative diseases such as Parkinson’s disease, and has been shown to protect neurons and promote regeneration after spinal cord and peripheral nerve injury. While GDNF has therapeutic potential for the treatment of nervous system disorders, it is a large protein which is costly to manufacture and difficult to administer to body tissues. The UCL team successfully developed peptides that mimic GDNF, binding to the same receptor and activating the same cellular responses, but without the challenges associated with using GDNF itself. 

Cells respond to the identified peptides in the same way as to the natural GDNF protein.

Cells respond to the identified peptides in the same way as to the natural GDNF protein.

Peptides are small biological molecules made from amino acids, the building blocks of proteins. The UCL team used high-throughput screening and computational modelling to select and refine peptides capable of binding to the GDNF receptor. The lead peptides were synthesised and shown to bind with high affinity to the GDNF receptor. Experiments were conducted using cell cultures, which responded to the peptides in the same way as to the natural GDNF protein, activating a signalling pathway associated with survival and regeneration. When the peptides were added to neurons growing in culture, they enhanced regeneration to the same extent as GDNF. 

Lead author Dr Emily Atkinson said “By using a combination of experimental and computational techniques we were able to identify peptides that bind strongly to GDNF receptors on the surface of cells and trigger the same cellular responses seen with the natural protein.”

Dr Rachael Dickman, one of the principal investigators and Lecturer in Drug Discovery said “Because peptides are smaller and more stable than growth factors they have the potential to be used therapeutically, being easier to produce on large scale and more easily delivered to tissues in a controlled manner.”

Professor James Phillips, Professor of Regenerative Medicine said “Being able to activate natural regenerative signalling in cells using peptides that mimic growth factors offers an exciting new opportunity to improve tissue regeneration following damage, particularly in the nervous system where there is a clear unmet clinical need.” 

The study, published in the Journal of Medicinal Chemistry, brought together experts from different departments and disciplines within the UCL School of Pharmacy, Department of Chemistry and Centre for Nerve Engineering and was mainly supported by funding from the EPSRC Centre for Doctoral Training in Transformative Pharmaceutical Technologies. 

External link to the paper: 

EA Atkinson, T Liu, M Fowler, PO Smith, AB Tabor, CJ Morris, JB Phillips & R Dickman (2026) Peptides Targeting GDNF Family Receptor Alpha 1 (GFRα1) Mimic Glial Cell Line-Derived Neurotrophic Factor (GDNF) Bioactivity. J Med Chem https://doi.org/10.1021/acs.jmedchem.5c03413 

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