Plasma proteomics identifies potential drug targets for diabetic polyneuropathy: Evidence from prospective cohorts and genetic analysis
Diabetes, Obesity and Metabolism, 2025
Lan H., Xu S., Li H., Guo R., Ma D., Feng Z., Wang Y.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Metabolic Diseases Neurology | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
Aims
Effective, targeted drug therapies for diabetic polyneuropathy (DP) are currently lacking. This study was designed to pinpoint new drug targets to enhance treatment efficacy.
Materials and Methods
Using large‐scale clinical and genetic datasets, we scrutinised proteins potentially involved in the onset and progression of DP . We further probed their associations with clinical symptoms and risk factors, and explored potential pathogenic mechanisms via single‐cell sequencing.
Results
We identified six proteins linked to DP , with Tumour Necrosis Factor Receptor Superfamily Member 14 ( TNFRSF14 ) standing out as a particularly compelling target. Notably, TNFRSF14 levels correlated with clinical scale (as assessed by the Michigan Neuropathy Screening Instrument) and might mediate the impact of metabolic syndrome on DP . At the cellular level, single‐cell sequencing hinted that TNFRSF14 could drive DP progression by activating macrophages and compromising endothelial cell function.
Conclusions
TNFRSF14 emerges as a promising biomarker and therapeutic target for the early detection and specific treatment of DP, paving the way for improved patient outcomes.