A biomarker-guided therapeutic map for alopecia: in vivo evidence and clinical implications.

Abstract

Alopecia is a multifactorial disorder involving disruption of immune, oxidative, apoptotic, and regenerative pathways in the hair follicle microenvironment. Despite therapeutic advances, clinical responses remain inconsistent, partly due to the limited understanding of underlying molecular targets. Integrating biomarker data may help clarify disease mechanisms and guide more targeted interventions. This review synthesizes in vivo animal evidence on six key biomarkers-tumor necrosis factor (TNF)-α, interleukin (IL)-6, malondialdehyde (MDA), caspase-3, vascular endothelial growth factor (VEGF), and β-catenin-and integrates their therapeutic implications into a biomarker-centered framework. A systematic search identified 15 animal studies (2014-2024) evaluating these biomarkers in alopecia models. TNF-α and IL-6 were generally elevated, indicating inflammation and immune-mediated follicular damage, whereas MDA reflected oxidative stress and caspase-3 activation marked apoptosis-driven regression. In contrast, VEGF and β-catenin were suppressed in alopecia but restored by effective interventions, supporting angiogenesis and Wnt-mediated regeneration. Various therapeutic approaches, including botanical extracts, bioactive compounds, sustained-release finasteride, microneedling, and nanoparticle-based delivery systems, were shown to reduce destructive biomarkers while enhancing regenerative pathways. Overall, alopecia can be conceptualized as an imbalance between degenerative and regenerative mechanisms, and a biomarker-guided therapeutic map may provide a useful translational framework for developing more precise and multitargeted treatment strategies.