ARG1-polyamine axis: cell-type-specific functions in disease pathogenesis and therapeutic targeting

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• Arginase 1 (ARG1) catalyzes L-arginine to L-ornithine, urea, polyamines, and L-proline.
• This enzymatic activity is crucial for nitrogen detoxification and has diverse tissue-specific functions.

Purpose of the Study:

• To review the context-dependent functions of ARG1 across various cell types.
• To explore ARG1's roles in tumorigenesis, immune modulation, vascular dysfunction, and wound healing.
• To highlight emerging therapeutic strategies targeting ARG1.

Main Methods:

• Literature review of ARG1's functions in different cell types and pathologies.
• Analysis of ARG1's metabolic networks and spatiotemporal roles.
• Examination of preclinical data for ARG1-targeted therapies.

Main Results:

• ARG1 exhibits context-dependent roles, driving immunosuppression and metabolic reprogramming in tumors, but can also suppress tumorigenesis.
• ARG1 influences immune cell differentiation, macrophage polarization, and microbiota interactions, affecting infection and autoimmunity.
• Endothelial ARG1 contributes to obesity-related vascular dysfunction, while keratinocyte ARG1 impacts wound healing and psoriasis.

Conclusions:

• ARG1 possesses dual roles in complex pathologies, acting as a central player in disease development and progression.
• Targeting ARG1 through inhibitors, engineered vesicles, or microbiome interventions shows therapeutic promise for cancer, cardiovascular, and neurodegenerative diseases.
• Mapping ARG1's metabolic networks is key for developing precision medicine strategies.