Androgenetic alopecia: combing the hair follicle signaling pathways for new therapeutic targets and more effective treatment options
September 2019
in “Expert Opinion on Therapeutic Targets”

TLDR
New treatments for hair loss may target specific pathways and generate new hair follicles.
This document is a review of potential targets for drug development to treat hair loss in androgenetic alopecia (AGA). The authors explore the signaling pathways involved in hair follicle development and cycling, with a focus on AGA. They suggest targeting BMP antagonism, Wnt antagonists, prostaglandins, and FGF family members as potential approaches for treating AGA. The authors also discuss the potential for hair neogenesis, or the generation of new hair follicles in situ, through injection of relevant morphogenic factors or cell populations. Overall, the document provides a comprehensive overview of the current state of research on androgenetic alopecia and potential therapeutic targets for treatment.
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Cited in this study

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research Viable terminal scalp hair follicles constitute a necessary and sufficient biological end‐organ that conditions clinical efficacy of finasteride in males with male pattern hair loss without implying reversal of miniaturized follicles
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research CXXC5: A novel regulator and coordinator of TGF-β, BMP and Wnt signaling
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research Hedgehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing
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research A bald statement - Current approaches to manipulate miniaturisation focus only on promoting hair growth
research Inducing hair follicle neogenesis with secreted proteins enriched in embryonic skin

research A hypothetical pathogenesis model for androgenic alopecia: clarifying the dihydrotestosterone paradox and rate-limiting recovery factors
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research Identification of Functional Patterns of Androgenetic Alopecia Using Transcriptome Profiling in Distinct Locations of Hair Follicles
AGA linked to inflammation, stress, fibrosis, and disturbed hair follicle stem cells.
research Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis
Blocking a protein called CXXC5 with a specific peptide can stimulate hair regrowth and new hair growth in wounds.

research Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways
Hair loss involves immune responses, inflammation, and disrupted signaling pathways.
research Prostaglandin D2 Uses Components of ROS Signaling to Enhance Testosterone Production in Keratinocytes
research After Skin Wounding, Noncoding dsRNA Coordinates Prostaglandins and Wnts to Promote Regeneration
After skin is damaged, noncoding dsRNA helps prostaglandins and Wnts work together to repair tissue and promote hair growth.

research Macrophages induce AKT/β-catenin-dependent Lgr5+ stem cell activation and hair follicle regeneration through TNF
Macrophages help regrow hair by activating stem cells using AKT/β-catenin and TNF.

research Androgens modify Wnt agonists/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia
Androgens prevent hair growth by changing Wnt signals in cells.

research Topical application of the Wnt/β-catenin activator methyl vanillate increases hair count and hair mass index in women with androgenetic alopecia
Methyl vanillate spray increases hair count and hair mass in women with hair loss.

research Assessment of tissue levels of dickkopf-1 in androgenetic alopecia and alopecia areata
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research Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis

research Combined treatment with oral finasteride and topical minoxidil in male androgenetic alopecia: a randomized and comparative study in Chinese patients
Finasteride and minoxidil together work best for male hair loss.

research dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration
Damage to skin releases dsRNA, which activates TLR3 and helps in skin and hair follicle regeneration.
research Principles and mechanisms of regeneration in the mouse model for wound‐induced hair follicle neogenesis

research Oxidative Stress–Associated Senescence in Dermal Papilla Cells of Men with Androgenetic Alopecia
Oxidative stress affects hair loss in men with androgenetic alopecia.
research Neuroendocrinology of the hair follicle: principles and clinical perspectives

research Topical valproic acid increases the hair count in male patients with androgenetic alopecia: A randomized, comparative, clinical feasibility study using phototrichogram analysis
Valproic acid increases hair count in men with hair loss.

research Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth
Growing human skin cells in a 3D environment can stimulate new hair growth.
research Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding
research Prostaglandin D2 Inhibits Wound-Induced Hair Follicle Neogenesis through the Receptor, Gpr44

research Skin shedding and tissue regeneration in African spiny mice (Acomys)
African spiny mice can regenerate skin, hair, and cartilage, but not muscle, and their unique abilities could be useful for regenerative medicine.
research New Activators and Inhibitors in the Hair Cycle Clock: Targeting Stem Cells’ State of Competence

research Prostaglandin D 2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia
PGD2 stops hair growth and is higher in bald men with AGA.
research Self-Organizing and Stochastic Behaviors During the Regeneration of Hair Stem Cells
research Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells
Men with baldness due to androgenetic alopecia still have hair stem cells, but lack specific cells needed for hair growth.

research A Mouse Model of Androgenetic Alopecia
Mice with human gene experienced hair loss when treated with DHT.
research Dihydrotestosterone-Inducible Dickkopf 1 from Balding Dermal Papilla Cells Causes Apoptosis in Follicular Keratinocytes

research Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding
Hair follicles can regrow in wounded adult mouse skin using a process like embryo development.

research Perifollicular Fibrosis: Pathogenetic Role in Androgenetic Alopecia
Androgen hormones cause hair follicle scarring in hair loss, and finasteride helps reduce it.

research Minoxidil: mechanisms of action on hair growth
Minoxidil boosts hair growth by opening potassium channels and increasing cell activity.

research Androgenetic alopecia: pathogenesis and potential for therapy
Hair loss needs more research for better treatments.

research Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss
Hair loss occurs due to fewer papillary cells, smaller follicles, and shorter growth phases.

research Measuring Reversal of Hair Miniaturization in Androgenetic Alopecia by Follicular Counts in Horizontal Sections of Serial Scalp Biopsies: Results of Finasteride 1mg Treatment of Men and Postmenopausal Women
Finasteride 1mg helps reverse hair miniaturization in men and postmenopausal women.

research Activation of Cytoprotective Prostaglandin Synthase-1 by Minoxidil as a Possible Explanation for Its Hair Growth-Stimulating Effect
Minoxidil boosts hair growth by activating PGHS-1.

research Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia
Horizontal scalp biopsy sections effectively diagnose and predict MPAA, with follicular density and inflammation impacting hair regrowth.
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research Maintenance of optimised hair growth from viable terminal scalp hair follicles at baseline with oral finasteride in male pattern hair loss and first evidence of a “drug dependency” and a post-finasteride “rebound effect”.
Finasteride helps hair growth but stopping it causes faster hair loss.

research Androgenetic alopecia: combing the hair follicle signaling pathways for new therapeutic targets and more effective treatment options
New treatments for hair loss may target specific pathways and generate new hair follicles.

research Androgenetic alopecia: pathogenesis and potential for therapy
Hair loss needs more research for better treatments.

research Finasteride increases anagen hair in men with androgenetic alopecia
Finasteride helps increase hair growth in men with hair loss.