In a recent review published in Genes & Diseases, researchers from Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing Key Laboratory of Neuro-Innovative Drug Research and Development of Traditional Chinese Medicine (Natural Medicines), Key Laboratory of Bioactive Substances and Resource Utilisation of Chinese Herbal Medicine, and Henan University of Chinese Medicine provide a comprehensive overview of the enzymatic, physiological, and pathological roles of CNDP1 and CNDP2, positioning these enzymes as emerging therapeutic targets across a spectrum of diseases.

The authors outline how CNDP1 (serum carnosinase) and CNDP2 (cytosolic non-specific dipeptidase), once thought to function solely in carnosine metabolism, have now been implicated in broader cellular processes including oxidative stress response, amino acid regulation, and dipeptide signalling.

Notably, CNDP2 catalyses the synthesis of N-lactoyl-phenylalanine (Lac-Phe) - a metabolite that suppresses appetite and obesity - linking CNDP function to energy balance and metabolic homeostasis.

This discovery reveals how enzymatic regulation of dipeptide metabolism may directly influence obesity and diabetes management.

The review also details the genetic polymorphisms and molecular mechanisms through which CNDP1 contributes to diabetic nephropathy, identifying it as a protective biomarker and potential therapeutic target for kidney-related complications in diabetes.

Moreover, CNDP2’s diverse activity spectrum extends to cancer, where it exhibits context-dependent functions - acting as a tumour suppressor in gastric cancer by activating the MAPK pathway, while showing upregulated expression in renal and colorectal cancers, suggesting its utility as an early diagnostic biomarker.

Importantly, CNDP1 also influences tumour immune regulation through the miR-135b-5p/CNDP1 axis in hepatocellular carcinoma, underscoring its role in modulating immune checkpoint activity and tumour microenvironment interactions.

Together, these findings establish CNDP enzymes as key molecular bridges between metabolic disorders and oncogenic pathways.

The authors propose that future studies focusing on CNDP-regulated signalling networks, genetic variants, and metabolite dynamics could open new avenues for developing targeted therapies and diagnostic tools for diseases driven by metabolic dysregulation and abnormal proteostasis.

Source: Compuscript Ltd