Functionalized retinoid

Recent reports also indicate that some synthetic retinoids act through other signalling pathways that do not involve the retinoid receptors. For example, V-(4-hydroxyphenyl) dX -trans-retinamide (4-HPR), which is currently undergoing clinical trials for prevention of breast cancer and which is reported to prevent ovarian cancer [37], appears to function through an anti-oxidant pathway to induce cancer cell apoptosis [38]. 6-[3-(l-Adamantyl)-4-hydrox-yphenyl]-2-naphthalenecarboxylic acid (AHPN, CD437) is able to induce cell cycle arrest and apoptosis in cancer cell lines that lack functional retinoid receptors and do not respond to growth... 

Systemic treatment of 13-cis retinoic acid frequently leads to cheilitis and eye irritations (e.g., unspecific cornea inflammation). Also other symptoms such as headache, pruritus, alopecia, pains of joints and bone, and exostosis formation have been reported. Notably, an increase of very low density lipoproteins and triglycerides accompanied by a decrease of the high density lipoproteins has been reported in 10-20% of treated patients. Transiently, liver function markers can increase during oral retinoid therapy. Etretinate causes the side effects of 13-cis retinoid acid at lower doses. In addition to this, generalized edema and centrilobulary toxic liver cell necrosis have been observed. 

Gene regulation by tocopherols has mainly been associated with PKC because of its deactivation by a-tocopherol and its contribution in the regulation of a number of transcription factors (NF-kappaB, API). A direct participation of the pregnane X receptor (PXR)/ retinoid X receptor (RXR) has been also shown. The antioxidant-responsive element (ARE) and the TGF-beta-responsive element appear in some cases to be implicated as well. The obser ved immunmodulatory function of a-tocopherol may also be attributed to the fact that the release of the proinflammatory cytokine interlukin-l 3 can be inhibited by a-tocopherol via... 

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

Vitamin A (retinol) and retinoic acid are carotenoid oxidation compounds that are very important for human health. The main functions of retinoids relate to vision and cellular differentiation. With the exception of retinoids, it was only about 10 years ago that other carotenoid oxidation products were first thought to possibly exert biological effects in humans and were implicated in the prevention - or promotion of degenerative diseases. A review on this subject was recently published. ... 

The retina comprises two principal components, the non-neural retinal pigment epithelium and the neural retina. The retinal pigment epithelium is an essential component of the visual system both structurally and functionally. It is important for the turnover and phagocytosis of photoreceptor outer segments, the metabolism of retinoids, the exchange of nutrients between the photoreceptors, and the choroidal blood vessels and the maintenance of an efficient outer blood-retinal barrier. 

Topical therapy is the initial drug treatment strategy for patients with mild to moderate psoriasis. It is estimated that approximately 70% to 80% of all patients with psoriasis can he treated adequately with use of topical therapy.1 Topical therapies include corticosteroids, coal tar products, anthralin, vitamin D3 analogues such as calcipotriol, retinoids such as tazarotene, and topical immunomodulators such as tacrolimus and pime-crolimus.18 Vitamin D3 analogues and topical retinoids all affect keratinocyte functions and the immune response. Currently, these are in wider use than is either anthralin or coal tar preparations. 

Blomhoff, R and Blomhoff, HK, 2006. Overview of retinoid metabolism and function. J Neurobiol 66, 606-630. 

Upregulation of retinoid receptor expression and function by provitamin A carotenoids may play a role in mediating the growth inhibitory effects of retinoids in cancer cells (Lian et al. 2006, Prakash et al. 2004). However, it is unclear if non-provitamin A carotenoids and their metabolites may act... 

Kennedy, M.W., Brass, A., McCruden, A.B., Price, N.C., Kelly, S.M. and Cooper, A. (1995b) The ABA-1 allergen of the parasitic nematode Ascaris suum fatty acid and retinoid binding function and structural characterization. Biochemistry 34, 6700-6710. 

Fig. 4-11). Interestingly, the larger amounts of P2 protein that are in myelin of some species correlate with increased widths of the major dense lines as determined by X-ray diffraction, and there appears to be substantially more P2 in large sheaths than small ones [4]. The large variation in the amount and distribution of the protein from species to species and sheath to sheath raises so far unanswered questions about its function. Its similarities to cytoplasmic proteins in other cells, whose functions appear to involve solubilization and transport of fatty acids and retinoids, suggest that it might function similarly in myelin assembly or turnover, but there is currently no direct experimental evidence to support this hypothesis. 

The interphotoreceptor retinoid-binding protein (Borst et al., 1989) functions in the regeneration of rhodopsin in the mammalian visual cycle. It is exclusive to vertebrates yet contains a repeated structure that has been found singly in bacterial and plant tail-specific proteases (TSPc) (Silber et al., 1992) and the archaeal tricorn protease (Tamura et al., 1996). The eukaryotic homologs of TSPc are likely to be inactive as... 

Pharmacology Isotretinoin is a retinoid that, when administered in pharmacologic dosages of 0.5 to 1 mg/kg/day, inhibits sebaceous gland function and keratinization. The exact mechanism of action of isotretinoin is unknown. 

Isotretinoin, or 13-cis-retinoic acid, and etretinate are available for oral administration. Isotretinoin is a synthetic retinoid that is used for sever cystic acne, recalcitrant to standard therapies. Its mechanism of action is not well understood but involves the inhibition of sebaceous gland size and function. 

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