Nanozyme Catalysis Restores Hair Follicle Integrity by Reversing Peroxisomal Collapse

Area of Science:

• Cell Biology
• Molecular Biology
• Dermatology

Background:

• Mitochondrial defects are known causes of hair loss.
• The role of peroxisomal dysfunction in hair follicle aging and alopecia is largely unexplored.

Purpose of the Study:

• To investigate the role of peroxisomal dysfunction in hair follicle aging and alopecia.
• To explore nanozyme-based therapeutic strategies for alopecia by targeting peroxisomal function.

Main Methods:

• Transcriptomic analysis of human dermal papilla cells from alopecia patients.
• Analysis of Nudt7-deficient mice with disrupted peroxisomal lipid metabolism.
• Development and testing of catalytic nanozymes (HA-Hem) mimicking catalase activity.
• Assessment of nanozyme effects on hair follicle regeneration, oxidative stress, and metabolic pathways in murine models.
• Spatial transcriptomic analysis to evaluate regenerative programs.

Main Results:

• Alopecia patients exhibit downregulated peroxisome-associated pathways.
• Nudt7-deficient mice show hair thinning, follicle miniaturization, and increased oxidative stress due to peroxisomal dysfunction.
• Nanozyme treatment restored metabolic balance, reduced oxidative damage, and stimulated hair follicle regeneration.
• Nanozymes enhanced PPARα expression, boosting peroxisomal biogenesis and lipid metabolism, and improving peroxisome-mitochondria interactions.
• Nanozyme therapy demonstrated superior regenerative responses compared to minoxidil, particularly in immunodeficient models.

Conclusions:

• Peroxisomal dysfunction is a key factor in hair follicle aging and loss.
• Targeting peroxisomal function with nanozymes represents a promising therapeutic strategy for alopecia.
• Restoring metabolic and redox homeostasis via peroxisomal enhancement promotes hair follicle regeneration.