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Journal of Parkinson's Disease 2021Evidence shows that altered retinoic acid signaling may contribute to the pathogenesis and pathophysiology of Parkinson's disease (PD). Retinoic acid is the bioactive... (Review)
Review
Evidence shows that altered retinoic acid signaling may contribute to the pathogenesis and pathophysiology of Parkinson's disease (PD). Retinoic acid is the bioactive derivative of the lipophilic vitamin A. Vitamin A is involved in several important homeostatic processes, such as cell differentiation, antioxidant activity, inflammation and neuronal plasticity. The role of vitamin A and its derivatives in the pathogenesis and pathophysiology of neurodegenerative diseases, and their potential as therapeutics, has drawn attention for more than 10 years. However, the literature sits in disparate fields. Vitamin A could act at the crossroad of multiple environmental and genetic factors of PD. The purpose of this review is to outline what is known about the role of vitamin A metabolism in the pathogenesis and pathophysiology of PD. We examine key biological systems and mechanisms that are under the control of vitamin A and its derivatives, which are (or could be) exploited for therapeutic potential in PD: the survival of dopaminergic neurons, oxidative stress, neuroinflammation, circadian rhythms, homeostasis of the enteric nervous system, and hormonal systems. We focus on the pivotal role of ALDH1A1, an enzyme expressed by dopaminergic neurons for the detoxification of these neurons, which is under the control of retinoic acid. By providing an integrated summary, this review will guide future studies on the potential role of vitamin A in the management of symptoms, health and wellbeing for PD patients.
Topics: Dopaminergic Neurons; Humans; Neuroinflammatory Diseases; Parkinson Disease; Tretinoin; Vitamin A
PubMed: 34120916
DOI: 10.3233/JPD-212671 -
Developmental Biology Jul 2021Vertebrate rod and cone photoreceptors detect light via a specialized organelle called the outer segment. This structure is packed with light-sensitive molecules known... (Review)
Review
Vertebrate rod and cone photoreceptors detect light via a specialized organelle called the outer segment. This structure is packed with light-sensitive molecules known as visual pigments that consist of a G-protein-coupled, seven-transmembrane protein known as opsin, and a chromophore prosthetic group, either 11-cis retinal ('A') or 11-cis 3,4-didehydroretinal ('A'). The enzyme cyp27c1 converts A into A in the retinal pigment epithelium. Replacing A with A in a visual pigment red-shifts its spectral sensitivity and broadens its bandwidth of absorption at the expense of decreased photosensitivity and increased thermal noise. The use of vitamin A-based visual pigments is strongly associated with the occupation of aquatic habitats in which the ambient light is red-shifted. By modulating the A/A ratio in the retina, an organism can dynamically tune the spectral sensitivity of the visual system to better match the predominant wavelengths of light in its environment. As many as a quarter of all vertebrate species utilize A, at least during a part of their life cycle or under certain environmental conditions. A utilization therefore represents an important and widespread mechanism of sensory plasticity. This review provides an up-to-date account of the A/A chromophore exchange system.
Topics: Animals; Opsins; Photoreceptor Cells, Vertebrate; Retina; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Retinal Pigments; Retinal Rod Photoreceptor Cells; Rod Opsins; Vitamin A
PubMed: 33684435
DOI: 10.1016/j.ydbio.2021.03.002 -
Nutrients Jun 2021The association between obesity and vitamin A has been studied. Some studies point to the anti-obesity activity related to this vitamin, carotenoids with provitamin A... (Review)
Review
The association between obesity and vitamin A has been studied. Some studies point to the anti-obesity activity related to this vitamin, carotenoids with provitamin A activity, and carotenoid conversion products. This performance has been evaluated in respect of adipogenesis, metabolic activity, oxidation processes, secretory function, and oxidative stress modulation, showing a new property attributed to vitamin A in preventing and treating obesity. However, vitamin A and its precursors are highly sensitive and easily degraded when subjected to heat, the presence of light, and oxygen, in addition to losses related to the processes of digestion and absorption. In this context, encapsulation presents itself as an alternative capable of increasing vitamin A's stability in the face of unfavorable conditions in the environment, which can reduce its functionality. Considering that vitamin A's status shows a strong correlation with obesity and is an innovative theme, this article addresses the associations between vitamin A's consumption and its precursors, encapsulated or not, and its physiological effects on obesity. The present narrative review points out those recent studies that demonstrate that vitamin A and its encapsulated precursors have the most preserved functionality, which guarantees better effects on obesity therapy.
Topics: Carotenoids; Drug Delivery Systems; Humans; Obesity; Vitamin A; Vitamins
PubMed: 34204998
DOI: 10.3390/nu13061921 -
Methods in Enzymology 2020Vitamin A signaling pathways are predominantly driven by the cellular concentrations of all-trans-retinoic acid (atRA), as the main mechanism of retinoid signaling is...
Vitamin A signaling pathways are predominantly driven by the cellular concentrations of all-trans-retinoic acid (atRA), as the main mechanism of retinoid signaling is via activation of retinoic acid receptors. atRA concentrations are in turn controlled by the storage of vitamin A and enzymatic processes that synthesize and clear atRA. This has resulted in the need for robust and highly specific analytical methods to accurately quantify retinoids in diverse biological matrices. Tissue-specific differences in both the quantity of retinoids and background matrix interferences can confound the quantification of retinoids, and the bioanalysis requires high performance instrumentation, such as liquid chromatography mass-spectrometry (LC-MS). Successful bioanalysis of retinoids is further complicated by the innate structural instability of retinoids and their relatively high lipophilicity. Further, in vitro experiments with retinoids require attention to experimental design and interpretation to account for the instability of retinoids due to isomerization and degradation, sequential metabolism to numerous structurally similar metabolites, and substrate depletion during experiments. In addition, in vitro biological activity is often confounded by residual presence of retinoids in common biological reagents such as cell culture media. This chapter identifies common biological and analytical complexities in retinoid bioanalysis in diverse biological matrices, and in the use of retinoids in cell culture and metabolic incubations. In addition, this chapter highlights best practices for the successful detection and quantification of the vitamin A metabolome in a wide range of biological matrices.
Topics: Receptors, Retinoic Acid; Retinoids; Signal Transduction; Tretinoin; Vitamin A
PubMed: 32359651
DOI: 10.1016/bs.mie.2020.02.010 -
Nutrients Oct 2022All-trans-retinoic acid (RA), a metabolite of vitamin A (retinol), exerts profuse actions that enable multiple aspects of reproduction, embryonic development and...
All-trans-retinoic acid (RA), a metabolite of vitamin A (retinol), exerts profuse actions that enable multiple aspects of reproduction, embryonic development and post-natal regulation of energy metabolism, glucoregulatory control, organ function, and of the skeletal, immune, nervous and cardiovascular systems, as well as cell proliferation vs [...].
Topics: Pregnancy; Female; Humans; Tretinoin; Vitamin A; Autacoids
PubMed: 36364786
DOI: 10.3390/nu14214526 -
TheScientificWorldJournal 2016Vitamin A is essential for life in all vertebrate animals. Vitamin A requirement can be met from dietary preformed vitamin A or provitamin A carotenoids, the most... (Review)
Review
Vitamin A is essential for life in all vertebrate animals. Vitamin A requirement can be met from dietary preformed vitamin A or provitamin A carotenoids, the most important of which is -carotene. The metabolism of -carotene, including its intestinal absorption, accumulation in tissues, and conversion to vitamin A, varies widely across animal species and determines the role that -carotene plays in meeting vitamin A requirement. This review begins with a brief discussion of vitamin A, with an emphasis on species differences in metabolism. A more detailed discussion of -carotene follows, with a focus on factors impacting bioavailability and its conversion to vitamin A. Finally, the literature on how animals utilize -carotene is reviewed individually for several species and classes of animals. We conclude that -carotene conversion to vitamin A is variable and dependent on a number of factors, which are important to consider in the formulation and assessment of diets. Omnivores and herbivores are more efficient at converting -carotene to vitamin A than carnivores. Absorption and accumulation of -carotene in tissues vary with species and are poorly understood. More comparative and mechanistic studies are required in this area to improve the understanding of -carotene metabolism.
Topics: Animals; Diet; Intestinal Absorption; Vitamin A; beta Carotene
PubMed: 27833936
DOI: 10.1155/2016/7393620 -
Wiley Interdisciplinary Reviews.... May 2017Vitamin A and its active metabolite retinoic acid are essential for embryonic development and adult homeostasis. Surprisingly, excess or deficiency of vitamin A and... (Review)
Review
Vitamin A and its active metabolite retinoic acid are essential for embryonic development and adult homeostasis. Surprisingly, excess or deficiency of vitamin A and retinoic acid can cause similar developmental defects. Therefore, strict feedback and other mechanisms exist to regulate the levels of retinoic acid within a narrow physiological range. The oxidation of vitamin A to retinal has recently been established as a critical nodal point in the synthesis of retinoic acid, and over the past decade, RDH10 and DHRS3 have emerged as the predominant enzymes that regulate this reversible reaction. Together they form a codependent complex that facilitates negative feedback maintenance of retinoic acid levels and thus guard against the effects of dysregulated vitamin A metabolism and retinoic acid synthesis. This review focuses on advances in our understanding of the roles of Rdh10 and Dhrs3 and their impact on development and disease. WIREs Dev Biol 2017, 6:e264. doi: 10.1002/wdev.264 For further resources related to this article, please visit the WIREs website.
Topics: Animals; Embryonic Development; Homeostasis; Humans; Signal Transduction; Vitamin A
PubMed: 28207193
DOI: 10.1002/wdev.264 -
Molecular Nutrition & Food Research Apr 2010Retinoid acid, the bioactive metabolite of vitamin A, is a potent signaling molecule in the brains of growing and adult animals, regulates numerous gene products, and... (Review)
Review
Retinoid acid, the bioactive metabolite of vitamin A, is a potent signaling molecule in the brains of growing and adult animals, regulates numerous gene products, and modulates neurogenesis, neuronal survival and synaptic plasticity. Vitamin A deficiency (VAD) is a global health problem, yet our knowledge of its effects on behavior and learning is still emerging. Here we review studies that have implicated retinoids in learning and memory deficits of post-embryonic and adult rodent and songbird models. Dietary vitamin A supplementation improves learning and memory in VAD rodents and can ameliorate cognitive declines associated with normal aging. Songbird studies examine the effects of retinoid signaling on vocal/auditory learning and are uniquely suited to study the behavioral effects of VAD because the neural circuitry of the song system is discrete and well understood. Similar to human speech acquisition, avian vocal learning proceeds in well-defined stages of template acquisition, rendition and maturation. Local blockade of retinoic acid production in the brain or excess dietary retinoic acid results in the failure of song maturation, yet does not affect prior song acquisition. Together these results yield significant insights into the role of vitamin A in maintaining neuronal plasticity and cognitive function in adulthood.
Topics: Animals; Behavior, Animal; Brain; Learning; Mice; Mice, Knockout; Models, Animal; Neuronal Plasticity; Neurotransmitter Agents; Songbirds; Tretinoin; Vitamin A; Vitamin A Deficiency; Vocalization, Animal
PubMed: 20077419
DOI: 10.1002/mnfr.200900246 -
Cellular and Molecular Life Sciences :... Jul 2003Beyond their classical nutritional roles, nutrients modify gene expression and function in target cells and, by so doing, affect many fundamental biological processes.... (Review)
Review
Beyond their classical nutritional roles, nutrients modify gene expression and function in target cells and, by so doing, affect many fundamental biological processes. An emerging example, which is the focus of this review, is the involvement of vitamin A in the regulation of the level and functioning of body fat reserves. Retinoic acid, the carboxylic acid form of vitamin A, is a transcriptional activator of the genes encoding uncoupling proteins, and results in animals indicate that whole body thermogenic capacity is related to the vitamin A status. Retinoic acid also influences adipocyte differentiation and survival, with high doses inhibiting and low doses promoting adipogenesis of preadipose cells in culture. Moreover, vitamin A status can influence the development and function of adipose tissues in whole animals, with a low vitamin A status favouring increased fat deposition.
Topics: Adipocytes; Adipose Tissue; Animals; Body Temperature Regulation; Homeostasis; Humans; Models, Biological; Receptors, Retinoic Acid; Vitamin A
PubMed: 12943220
DOI: 10.1007/s00018-003-2290-x -
Biological & Pharmaceutical Bulletin 2022Vitamin A is an important trace essential nutrient. Vitamin A is present as a retinyl ester in animal foods and as β-carotene (provitamin A), which is a precursor of... (Review)
Review
Vitamin A is an important trace essential nutrient. Vitamin A is present as a retinyl ester in animal foods and as β-carotene (provitamin A), which is a precursor of vitamin A, in plant foods such as green and yellow vegetables. After ingestion and absorption in the body, these are converted into retinol and stored as retinyl esters in stellate cells in the liver. The stored retinyl esters are decomposed into retinol as needed, and converted into the aldehyde retinal, which plays an important role in vision. Retinoic acid (RA) has a variety of effects. In particular, RA is used as a therapeutic agent for acute promyelocytic leukemia. This review will cover (1) elucidation of anti-refractory cancer effects of retinol (vitamin A) not mediated by RA receptors, (2) elucidation of anti-cancer effects of RA not mediated by RA receptors and (3) the development of candidate new anti-cancer agents that combine the actions of RA and retinol. Lessons learned from these findings are that vitamin A has anti-cancer activity not mediated by RA receptors; that nutritional management of vitamin A leads to prevention and treatment of cancer, and that new compounds developed from RA derivatives represent good anti-cancer drug candidates that are in various stages of clinical trials.
Topics: Animals; Antineoplastic Agents; Cell Transformation, Neoplastic; Liver; Neoplasms; Receptors, Retinoic Acid; Retinyl Esters; Tretinoin; Vitamin A
PubMed: 36047189
DOI: 10.1248/bpb.b22-00315