Pathogenic Mechanisms and Mechanism‐Directed Therapies for Androgenetic Alopecia: Current Understanding and Future Directions

Androgenetic alopecia (AGA) affects about half of men and many women worldwide, yet current treatments often fall short. This review summarizes key pathogenic mechanisms of AGA, centering on three interconnected processes: the dihydrotestosterone–prostaglandin D2 (DHT–PGD2) loop, oxidative stress and inflammation, and lipid metabolism dysregulation. These factors converge to suppress Wnt/β‐catenin signaling, the core pathway for hair growth. DHT and PGD2 reinforce each other to drive follicular miniaturization via CXXC5 and GSK‐3β activation. Oxidative stress and chronic inflammation—exacerbated by scalp microbiome imbalance, notably excess Cutibacterium acnes and Malassezia—further damage the follicular environment. Suppressed PPARγ signaling disrupts adipocyte‐follicle crosstalk, reducing growth factor support. These insights reveal emerging therapeutic targets, including DP2 antagonists, CXXC5/GSK‐3β inhibitors, antioxidants, microbiome modulators, and PPARγ agonists. By integrating molecular, microbial, and metabolic perspectives, this review outlines a framework for multitarget strategies to address the limitations of existing AGA treatments.

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Publication Details

Journal
Dermatologic Therapy
Published
2025-01-01
DOI
https://doi.org/10.1155/dth/9950475
Citations
4
Primary Topic
Hair Growth and Disorders
Type
article
Field-Weighted Citation Impact
7.35

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article

Pathogenic Mechanisms and Mechanism‐Directed Therapies for Androgenetic Alopecia: Current Understanding and Future Directions

X Q Li, H. Shi, Yanyan Feng, Xiaolin Wang
4 citations
Dermatologic Therapy
Hair Growth and Disorders
7.35
article

Pathogenic Mechanisms and Mechanism‐Directed Therapies for Androgenetic Alopecia: Current Understanding and Future Directions

X Q Li, H. Shi, Yanyan Feng, Xiaolin Wang
article en
4 citations

Abstract

Androgenetic alopecia (AGA) affects about half of men and many women worldwide, yet current treatments often fall short. This review summarizes key pathogenic mechanisms of AGA, centering on three interconnected processes: the dihydrotestosterone–prostaglandin D2 (DHT–PGD2) loop, oxidative stress and inflammation, and lipid metabolism dysregulation. These factors converge to suppress Wnt/β‐catenin signaling, the core pathway for hair growth. DHT and PGD2 reinforce each other to drive follicular miniaturization via CXXC5 and GSK‐3β activation. Oxidative stress and chronic inflammation—exacerbated by scalp microbiome imbalance, notably excess Cutibacterium acnes and Malassezia—further damage the follicular environment. Suppressed PPARγ signaling disrupts adipocyte‐follicle crosstalk, reducing growth factor support. These insights reveal emerging therapeutic targets, including DP2 antagonists, CXXC5/GSK‐3β inhibitors, antioxidants, microbiome modulators, and PPARγ agonists. By integrating molecular, microbial, and metabolic perspectives, this review outlines a framework for multitarget strategies to address the limitations of existing AGA treatments.

Dermatologic TherapyVol. 2025(1)
Affiliated Hospital of Southwest Medical University (CN), Chengdu Second People's Hospital (CN)
Department of Science and Technology of Sichuan Province
Openalex Percentile: Top 3%
Hair Growth and Disorders
7.35
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