Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors and comprise three different isoforms namely PPARα, PPARγ, and PPARβ/δ with PPARβ/δ being the predominant subtype in human keratinocytes. After binding with specific ligands, PPARs regulate gene expression, cell growth and differentiation, apoptosis, inflammatory responses, and tumorogenesis. PPARs also modulate a wide variety of skin functions including keratinocyte proliferation, epidermal barrier formation, wound healing, melanocyte proliferation, and sebum production. Recent studies have shown the importance of PPARs in the pathogenesis of many dermatological disorders. Clinical trials have suggested possible role of PPAR agonists in the management of various dermatoses ranging from acne vulgaris, psoriasis, hirsutism, and lipodystrophy to cutaneous malignancies including melanoma. This article is intended to be a primer for dermatologists in their understanding of clinical relevance of PPARs and PPAR agonists in dermatology therapeutics.

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

“…Since all PPARs are widely expressed in human skin and its appendages, there is increasing interest in their role in maintaining cutaneous homeostasis and in dermatological disorders . PPAR‐mediated signalling has attracted special interest in psoriasis, atopic dermatitis, acne, skin ageing, scleroderma, melasma, lipodystrophy and skin cancer . In the context of this Focus Theme Issue , this development encourages one to also take a closer look at why and how exactly PPARs are of special interest in a translational hair research context, with a strict focus on their best‐investigated isoform, PPAR‐γ.…”

Cholesterol homeostasis: Links to hair follicle biology and hair disorders

“…Dysregulation or dysfunction in the PPAR family of ligand‐activated nuclear receptors is also suggested to be a causative factor in PCA . Regulation of cholesterol homeostasis is the domain of numerous nuclear hormone receptors and the PPARs represent one such important pathway . PPAR heterodimerisation with retinoid X receptor (RXR) initiates binding to PPRE (peroxisome proliferator response element), enhancing proliferation of peroxisomes, which act as secondary sites for cholesterol synthesis .…”

“…Regulation of cholesterol homeostasis is the domain of numerous nuclear hormone receptors and the PPARs represent one such important pathway . PPAR heterodimerisation with retinoid X receptor (RXR) initiates binding to PPRE (peroxisome proliferator response element), enhancing proliferation of peroxisomes, which act as secondary sites for cholesterol synthesis . Beyond lipid homeostasis, PPAR activation is also associated with immune regulation and anti‐inflammatory affects .…”

Activation of Peroxisome Proliferator-Activated Receptor Alpha Improves Aged and UV-Irradiated Skin by Catalase Induction

“…These PPAR isotypes share high degree of structural homology but differ in their functional roles and tissue expression. Although PPARβ/δ is the predominant isotype found in the skin, PPARα is also expressed in the skin, as well as in various tissues such as the liver, brown adipose tissue, heart, and kidney [19]. PPARα has an important role in the fatty acid oxidation, lipid and lipoprotein metabolism, inflammatory responses, and oxidative stress [20, 21].…”