Retinoids are compounds with pleiotropic functions and a relatively selective targeting of certain skin structures. They are
vitamins, because
retinol (
vitamin A) is not synthesized in the body and must be derived from diet, but also
hormones with intracrine activity, because
retinol is transformed into molecules that bind to
nuclear receptors, exhibit their activity, and are subsequently inactivated.
Retinoids exert their effects on target cells by binding and activating nuclear
retinoid receptors.
Retinoid receptors bind their
ligands in form of dimers. Heterodimers can be formed between two different
retinoid receptor molecules but also between
retinoid X receptors and the
vitamin D receptor as well as the triiodothyronin receptor. This fact indicates complex interactions between
retinoids and further hormonal signal transduction molecules. Interaction of
retinoid receptors with transcriptional factors activated by other signal transduction mechanisms, e.g.
AP-1, may provide dissociation of the
retinoid effects.
Retinoids can exhibit agonistic activity but also be neutral antagonists and inverse agonists. Topical and oral
retinol,
tretinoin,
isotretinoin, and
bexarotene, topical
alitretinoin,
retinaldehyde,
motretinide,
adapalene,
tazarotene, and
systemin acitretin compose the list of launched
retinoids.
Psoriasis and related
disorders, congenital disorders of keratinization,
acne, photoaging and hypovitaminosis A are classical approved indications of
retinoid treatment, whereas
cutaneous T-cell lymphoma,
AIDS-associated
Kaposi's sarcoma,
acute promyelocytic leukemia and actinic
lentigines were currently confirmed. In addition,
retinoids have been successfully used in several other
dermatoses, e.g. epithelial precanceroses and
tumors,
seborrhea,
rosacea and acneiform
dermatoses,
lichen planus, eosinophilic
folliculitis, condylomata accuminata,
lichen sclerosus and atrophicus. Highly receptor selective molecules,
retinoic acid receptor-beta-inducers,
AP-1 complex antagonists, and inverse agonists will be probably lead the
retinoid development in the near future. New, more effective and less toxic
retinoids, alone or in combination with other drugs and new delivery systems may provide therapeutic solutions for benign and malignant proliferative
skin diseases, such as
psoriasis and non-
melanoma tumors,
cancer chemoprevention and differentiation
therapy.