Cover Image: Neuroendocrine treatment of inherited keratin disorders by cannabinoids?

Ramot, Yuval; Oláh, Attila; Paus, Ralf

doi:10.1111/bjd.16570

Cited by 16 publications

(17 citation statements)

References 2 publications

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“…As reviewed above, the CB 1 agonist ACEA increased K10 expression, while reducing K1 production in human epidermis in culture [69]. Such changes could potentially be harnessed in epidermolytic ichthyosis patients to decrease the expression of mutated K1 while upregulating the expression of K10 that can functionally compensate in part for the mutated keratin.…”

Section: Treatment Of Keratin-related Skin and Hair Genetic Disordersmentioning

confidence: 92%

“…When tested in human skin culture and again in HaCaT cells, anandamide also inhibited K6 and K16 expression, independent of its antiproliferative properties [68]. Conversely, administration of the CB 1 antagonist, arachidonyl-2′-chloroethylamide (ACEA), upregulated K10 in human epidermis while decreasing the expression of K1 ex vivo [69].…”

Section: The Effects Of Endocannabinoids On Keratin Expressionmentioning

confidence: 99%

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Neuroendocrine Controls of Keratin Expression in Human Skin

Ramot¹,

Paus²

2018

Keratin

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The human skin serves as a source for a large number of neurohormones and neuropeptides, which affect skin biology on multiple different levels. Intriguingly, this includes the control of keratin expression by neurohormones such as thyrotropin-releasing hormone, thyrotropin, opioids, prolactin, and cannabinoid receptor 1-ligands. While this neuroendocrine regulation of human keratin biology in situ is likely to be involved in the maintenance of skin and hair follicle homeostasis and may participate in skin pathology, this regulation remains to be appreciated and explored by mainstream keratin research. Here, we review recent progress in this frontier of neuroendocrine and keratin skin research, define the many open questions in the field, and elaborate how neurohormones may be harnessed to treat selected genodermatoses and other skin disorders accompanied by abnormal keratin expression.

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Section: Treatment Of Keratin-related Skin and Hair Genetic Disordersmentioning

confidence: 92%

Section: The Effects Of Endocannabinoids On Keratin Expressionmentioning

confidence: 99%

Neuroendocrine Controls of Keratin Expression in Human Skin

Ramot¹,

Paus²

2018

Keratin

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“…The samples were obtained with informed patient consent and approval from the University of Muenster Ethics Committee, adhering to Helsinki guidelines. The samples were prepared as 4‐mm punch samples and used for full‐thickness human skin organ culture serum‐free conditions as described previously . The samples were kept free‐floating in serum‐free medium.…”

Section: Methodsmentioning

confidence: 99%

Theophylline exerts complex anti‐ageing and anti‐cytotoxicity effects in human skin ex vivo

Bertolini

Ramot

Gherardini

et al. 2019

Intern J of Cosmetic Sci

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OBJECTIVE: Theophylline is a phosphodiesterase inhibitor that is being used clinically for asthma therapy. In addition, it is recognized as a cosmetic agent with possible anti-ageing and anti-oxidative properties. Nevertheless, how it affects human skin is still poorly examined. METHODS: Theophylline (10 or 100 µM) was administered to the culture medium of full-thickness human skin ex vivo for 24 or 72 h. RESULTS: Theophylline stimulated protein expression of the antioxidant metallothionein-1 and mRNA levels of collagen I and III. Assessment of fibrillin-1 immunohistology revealed enhanced structural stability of dermal microfibrils. Theophylline also exerted extracellular matrix-protective effects by decreasing MMP-2 and MMP-9 mRNA levels, partially antagonizing the effects of menadione, the potent, toxic ROS donor. In addition, it decreased menadione-stimulated epidermal keratinocytes apoptosis. Interestingly, theophylline also increased the level of intracutaneously produced melatonin, that is the most potent ROS-protective and DNA damage repair neuromediator, and tendentially increased protein expression of MT1, the melatonin receptor. Theophylline also increased the expression of keratin 15, the stem cell marker, in the epidermal basal layer but did not change mitochondrial activity or epidermal pigmentation. CONCLUSION: This ex vivo pilot study in human skin shows that theophylline possesses several interesting complex skin-protective properties. It encourages further examination of theophylline as a topical candidate for anti-ageing treatment. R esum e OBJECTIF: la th eophylline est un inhibiteur de la phosphodiest erase actuellement utilis ee en clinique pour le traitement de l'asthme. En outre, elle est reconnue comme etant un agent cosm etique ayant des propri et es potentiellement anti-âge et antioxydantes. Cependant, la mani ere dont elle affecte la peau chez l'homme est encore tr es peu etudi ee. M ETHODES: de la th eophylline (10 ou 100 lM) a et e ajout ee dans le milieu de culture d'un echantillon de peau humaine d' epaisseur totale ex vivo pendant 24 ou 72 h. Theophylline effects in human skin ex vivo M. Bertolini et al. 84 Theophylline effects in human skin ex vivo M. Bertolini et al. Theophylline effects in human skin ex vivo M. Bertolini et al. Theophylline effects in human skin ex vivo M. Bertolini et al.

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“…Keratinization disorders result from mutations in one of the keratin genes, resulting in inherited skin or hair disorders, based on the expression pattern of the mutated keratin. 70,115,116 Since keratins form intermediate filaments by forming a heterodimer pair of keratins, it has been postulated that this keratin-modulating effect can be harnessed to upregulate the expression of non-mutated keratin genes or keratins that can compensate for the mutated, functionally defective keratin gene product and/or downregulate the mutated keratins. 70,115,116 This may suffice to counteract, at least in part, some of the functional defects imparted by the mutated keratin.…”

Section: Keratinization Disordersmentioning

confidence: 99%

“…70,115,116 Since keratins form intermediate filaments by forming a heterodimer pair of keratins, it has been postulated that this keratin-modulating effect can be harnessed to upregulate the expression of non-mutated keratin genes or keratins that can compensate for the mutated, functionally defective keratin gene product and/or downregulate the mutated keratins. 70,115,116 This may suffice to counteract, at least in part, some of the functional defects imparted by the mutated keratin. For example, the stimulatory effect of TH on K15 might be beneficial in patients with K14 mutations associated with epidermolysis bullosa simplex, since K15 can substitute for the mutated K14 in forming keratin pairs with K5.…”

Section: Keratinization Disordersmentioning

confidence: 99%

Topical L‐thyroxine: The Cinderella among hormones waiting to dance on the floor of dermatological therapy?

Paus

Ramot

Kirsner

et al. 2020

Experimental Dermatology

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Dermatologists have used natural or synthetic agonists of glucocorticoid, vitamin D or retinoid nuclear hormone receptors, both systemically and topically, for decades in the management of skin diseases. In fact, the introduction of glucocorticoids, calcitriols and retinoids into the clinic each constituted landmark progress in skin therapies, and the range of dermatological indications for each of these distinct classes of chemicals rapidly expanded after they became widely accepted in clinical practice. 1,2 Given the success of these agents, it is surprising that a fourth class of potent nuclear hormone receptor agonists has not been developed as part of the therapeutic arsenal of dermatology: endogenous and synthetic thyroid hormone receptor (TR) ligands. 3 This "Cinderella status" of these peptide hormones among endocrinological dermatotherapy is even more surprising in view of

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Cover Image: Neuroendocrine treatment of inherited keratin disorders by cannabinoids?

Cited by 16 publications

References 2 publications

Neuroendocrine Controls of Keratin Expression in Human Skin

Neuroendocrine Controls of Keratin Expression in Human Skin

Theophylline exerts complex anti‐ageing and anti‐cytotoxicity effects in human skin ex vivo

Topical L‐thyroxine: The Cinderella among hormones waiting to dance on the floor of dermatological therapy?

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