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Molecules (Basel, Switzerland) Mar 2020Direct sun exposure is one of the most aggressive factors for human skin. Sun radiation contains a range of the electromagnetic spectrum including UV light. In addition... (Review)
Review
Direct sun exposure is one of the most aggressive factors for human skin. Sun radiation contains a range of the electromagnetic spectrum including UV light. In addition to the stratospheric ozone layer filtering the most harmful UVC, human skin contains a photoprotective pigment called melanin to protect from UVB, UVA, and blue visible light. This pigment is a redox UV-absorbing agent and functions as a shield to prevent direct UV action on the DNA of epidermal cells. In addition, melanin indirectly scavenges reactive oxygenated species (ROS) formed during the UV-inducing oxidative stress on the skin. The amounts of melanin in the skin depend on the phototype. In most phenotypes, endogenous melanin is not enough for full protection, especially in the summertime. Thus, photoprotective molecules should be added to commercial sunscreens. These molecules should show UV-absorbing capacity to complement the intrinsic photoprotection of the cutaneous natural pigment. This review deals with (a) the use of exogenous melanin or melanin-related compounds to mimic endogenous melanin and (b) the use of a number of natural compounds from plants and marine organisms that can act as UV filters and ROS scavengers. These agents have antioxidant properties, but this feature usually is associated to skin-lightening action. In contrast, good photoprotectors would be able to enhance natural cutaneous pigmentation. This review examines flavonoids, one of the main groups of these agents, as well as new promising compounds with other chemical structures recently obtained from marine organisms.
Topics: Animals; Antioxidants; Aquatic Organisms; Flavonoids; Humans; Melanins; Oxidative Stress; Plants; Reactive Oxygen Species; Skin; Skin Pigmentation; Sunscreening Agents; Ultraviolet Rays
PubMed: 32230973
DOI: 10.3390/molecules25071537 -
Current Biology : CB Feb 2020Melanins are a unique class of pigments found throughout the biosphere with a wide variety of functions, structures, and presentations. Cordero and Casadevall highlight...
Melanins are a unique class of pigments found throughout the biosphere with a wide variety of functions, structures, and presentations. Cordero and Casadevall highlight the wide range of places melanins are found and the diverse functions they play in nature.
Topics: Melanins
PubMed: 32097632
DOI: 10.1016/j.cub.2019.12.042 -
Ageing Research Reviews Aug 2021Melanogenesis is a complex process in which melanin is synthesized in melanocytes and transported to keratinocytes, which involves multiple genes and signaling pathways.... (Review)
Review
Melanogenesis is a complex process in which melanin is synthesized in melanocytes and transported to keratinocytes, which involves multiple genes and signaling pathways. Epigenetics refers to the potential genetic changes that affect gene expression without involving changes in the original sequence of DNA nucleotides. DNA methylation regulates the expression of key genes such as tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase (DCT) and microphthalmia-associated transcription factor (MITF), as well as paracrine factors such as stem cell factor (SCF) and endothelin-1 (ET-1) in melanogenesis. Potential DNA methylation sites are present in the genes of melanogenesis-related signaling pathways such as "Wnt", "PI3K/Akt/CREB" and "MAPK". H3K27 acetylation is abundant in melanogenesis-related genes. Both the upstream activation and downstream regulation of MITF depend on histone acetyltransferase CBP/p300, and pH-induced H3K27 acetylation may be the amplifying mechanism of MITF's effect. HDAC1 and HDAC10 catalyze histone deacetylation of melanogenesis-related gene promoters. Chromatin remodelers SWI/SNF complex and ISWI complex use the energy of ATP hydrolysis to rearrange nucleosomes, while their active subunits BRG1, BRM and BPTF, act as activators and cofactors of MITF. MicroRNAs (miRNAs) can directly target a large number of melanogenesis-related genes, while long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) regulate melanogenesis in a variety of ways. Interactions exist among the epigenetic mechanisms of melanogenesis. For example, the methyl CpG binding domain protein 2 (MeCP2) links DNA methylation, histone deacetylation, and histone methylation. Epigenetic-based therapy provides novel opportunities for treating dermatoses that are caused by pigmentation disturbances. This review summarizes the epigenetic regulation mechanisms of melanogenesis, and examines the pathogenesis and treatment of epigenetics in pigmentation disorders.
Topics: Animals; Epigenesis, Genetic; Gene Expression Regulation; Humans; Melanins; Melanocytes
PubMed: 33984527
DOI: 10.1016/j.arr.2021.101349 -
Chembiochem : a European Journal of... Dec 2023This review introduces multifaceted mutual interactions between molecules containing a catechol moiety and aggregation-prone proteins. The complex relationships between... (Review)
Review
This review introduces multifaceted mutual interactions between molecules containing a catechol moiety and aggregation-prone proteins. The complex relationships between these two molecular species have previously been elucidated primarily in a unidirectional manner, as demonstrated in cases involving the development of catechol-based inhibitors for amyloid aggregation and the elucidation of the role of functional amyloid fibers in melanin biosynthesis. This review aims to consolidate scattered clues pertaining to catechol-based amyloid inhibitors, functional amyloid scaffold of melanin biosynthesis, and chemically designed peptide fibers for providing chemical insights into the role of the local three-dimensional orientation of functional groups in manifesting such interactions. These orientations may play crucial, yet undiscovered, roles in various supramolecular structures.
Topics: Amyloid beta-Peptides; Melanins; Amyloid; Amyloidogenic Proteins; Catechols
PubMed: 37850717
DOI: 10.1002/cbic.202300628 -
Progress in Retinal and Eye Research Nov 2022Albinism is a pigment disorder affecting eye, skin and/or hair. Patients usually have decreased melanin in affected tissues and suffer from severe visual abnormalities,... (Review)
Review
Albinism is a pigment disorder affecting eye, skin and/or hair. Patients usually have decreased melanin in affected tissues and suffer from severe visual abnormalities, including foveal hypoplasia and chiasmal misrouting. Combining our data with those of the literature, we propose a single functional genetic retinal signalling pathway that includes all 22 currently known human albinism disease genes. We hypothesise that defects affecting the genesis or function of different intra-cellular organelles, including melanosomes, cause syndromic forms of albinism (Hermansky-Pudlak (HPS) and Chediak-Higashi syndrome (CHS)). We put forward that specific melanosome impairments cause different forms of oculocutaneous albinism (OCA1-8). Further, we incorporate GPR143 that has been implicated in ocular albinism (OA1), characterised by a phenotype limited to the eye. Finally, we include the SLC38A8-associated disorder FHONDA that causes an even more restricted "albinism-related" ocular phenotype with foveal hypoplasia and chiasmal misrouting but without pigmentation defects. We propose the following retinal pigmentation pathway, with increasingly specific genetic and cellular defects causing an increasingly specific ocular phenotype: (HPS1-11/CHS: syndromic forms of albinism)-(OCA1-8: OCA)-(GPR143: OA1)-(SLC38A8: FHONDA). Beyond disease genes involvement, we also evaluate a range of (candidate) regulatory and signalling mechanisms affecting the activity of the pathway in retinal development, retinal pigmentation and albinism. We further suggest that the proposed pigmentation pathway is also involved in other retinal disorders, such as age-related macular degeneration. The hypotheses put forward in this report provide a framework for further systematic studies in albinism and melanin pigmentation disorders.
Topics: Humans; Melanins; Mutation; Albinism; Retina; Pigmentation
PubMed: 35729001
DOI: 10.1016/j.preteyeres.2022.101091 -
Journal of the American Chemical Society Mar 2021Commonly known as a skin pigment, melanin has a vital role in UV radiation protection, primarily acting as a radical scavenger. However, a lesser known natural property...
Commonly known as a skin pigment, melanin has a vital role in UV radiation protection, primarily acting as a radical scavenger. However, a lesser known natural property of melanin, observed in some melanized organisms, is its capacity to adsorb toxins, including metals and organic molecules. Inspired by this, we set out to generate a synthetic porous melanin that would pave the way to enhancing the natural adsorbent properties of melanin and melanin-like materials. Here, we developed a method for the synthesis of porous polydopamine-based melanin utilizing a mesoporous silica (MS) nanoparticle template and characterized its physical properties. Through the oxidative polymerization of dopamine, followed by the etching of silica, we generated synthetic porous melanin (SPM) with the highest measured surface area of any known polydopamine-based material. The prepared SPM was effective for the uptake of various gases and organophosphate toxins, with the material exhibiting high selectivity for CO over CH and high potential for ammonia capture. Given the demonstrated advantages provided by synthetic porous melanin and melanin's role as an adsorbent in nature, we anticipate the discovery of porous analogues in biological systems.
Topics: Carbon Dioxide; Indoles; Melanins; Methane; Polymers; Porosity
PubMed: 33600146
DOI: 10.1021/jacs.0c10465 -
Theranostics 2023Senescent melanocytes accumulate in photoaged skin and are closely related to skin aging. A better understanding of the molecular characteristics of senescent...
Senescent melanocytes accumulate in photoaged skin and are closely related to skin aging. A better understanding of the molecular characteristics of senescent melanocytes may be the key to controlling skin aging. We have developed an model of senescence in melanocytes using UV irradiation and investigated the functional characteristics and molecular mechanisms underlying senescence in UV-irradiated melanocytes. We have highlighted that senescent melanocytes are characterized by melanosome transport dysfunction resulting in melanin accumulation. The defective melanosome transport was confirmed with the ultrastructural characterization of both UV-induced senescent melanocytes and melanocytes of hypopigmented aging skin. A single-cell transcriptomic analysis revealed that the glycolytic metabolism pathway appeared to be significantly upregulated in most senescent phenotypes. Furthermore, the inhibition of glycolysis by pharmacological compounds mitigates the pro-aging effects of melanocytes senescence, suggesting that alterations in cellular glucose metabolism act as a driving force for senescence in melanocytes. These results demonstrate that senescent melanocytes are characterized by glycolytic metabolism changes and a defective melanosome transport process, which may be related to impaired mitochondrial function, highlighting the importance of metabolic reprogramming in regulating melanocyte senescence.
Topics: Melanosomes; Melanocytes; Skin; Melanins; Glycolysis; Cellular Senescence
PubMed: 37554281
DOI: 10.7150/thno.84912 -
International Journal of Molecular... Jun 2021Melanogenesis is the process leading to the synthesis of melanin, the main substance that influences skin color and plays a pivotal role against UV damage. Altered... (Review)
Review
Melanogenesis is the process leading to the synthesis of melanin, the main substance that influences skin color and plays a pivotal role against UV damage. Altered melanogenesis is observed in several pigmentation disorders. Melanogenesis occurs in specialized cells called melanocytes, physically and functionally related by means of autocrine and paracrine interplay to other skin cell types. Several external and internal factors control melanin biosynthesis and operate through different intracellular signaling pathways, which finally leads to the regulation of microphthalmia-associated transcription factor (), the key transcription factor involved in melanogenesis and the expression of the main melanogenic enzymes, including TYR, TYRP-1, and TYRP-2. Epigenetic factors, including microRNAs (miRNAs), are involved in melanogenesis regulation. miRNAs are small, single-stranded, non-coding RNAs, of approximately 22 nucleotides in length, which control cell behavior by regulating gene expression, mainly by binding the 3' untranslated region (3'-UTR) of target mRNAs. This review collects data on the miRNAs involved in melanogenesis and how these miRNAs can modulate target gene expression. Bringing to light the biological function of miRNAs could lead to a wider understanding of epigenetic melanogenesis regulation and its dysregulation. This knowledge may constitute the basis for developing innovative treatment approaches for pigmentation dysregulation.
Topics: Animals; Epigenesis, Genetic; Gene Expression Regulation; Humans; Melanins; Melanocytes; MicroRNAs; Microphthalmia-Associated Transcription Factor; Pigmentation Disorders; Skin Pigmentation
PubMed: 34198907
DOI: 10.3390/ijms22116104 -
World Journal of Microbiology &... Sep 2022Melanin is a secondary metabolite composed of complex heterogeneous polymers. Fungal melanin is considered to be a sustainable and biodegradable natural pigment and has... (Review)
Review
Melanin is a secondary metabolite composed of complex heterogeneous polymers. Fungal melanin is considered to be a sustainable and biodegradable natural pigment and has a variety of functional properties and biological activities. On one hand, due to its own specific properties it can play the role of antioxidant, anti-radiation, adsorption, and photoprotection. On the other hand, it has good biological activities such as hepatoprotective effect, hypolipidemic effect and anti-cancer. Therefore, it is widely used in various fields of daily life, including dyeing, food, biomedical and commercial industry. It is conducive to environmental protection and human health. However, the insolubility of fungal melanin in water, acids and organic solvents has been an obstacle to its commercial applications. Thus, the chemical modification methods of fungal melanin are summarized to increase its solubility and expand the application fields. Although fungal melanin has been used in many industries, as the structure and function of fungal melanin and modified melanin are further studied, more functional properties and bioactivities are expected to be discovered for a wide range of applications in the future.
Topics: Antioxidants; Fungi; Humans; Melanins; Polymers; Solvents; Water
PubMed: 36149606
DOI: 10.1007/s11274-022-03415-0 -
Journal of Nuclear Medicine : Official... May 2024Melanin is one of the representative biomarkers of malignant melanoma and a potential target for diagnosis and therapy. With advancements in chemistry and radiolabeling... (Review)
Review
Melanin is one of the representative biomarkers of malignant melanoma and a potential target for diagnosis and therapy. With advancements in chemistry and radiolabeling technologies, promising strides have been made to synthesize radiolabeled melanin-binding molecules for various applications. We present an overview of melanin-targeted radiolabeled molecules and compare their features reported in preclinical studies. Clinical practice and trials are also discussed to elaborate on the safety and validity of the probes, and expanded applications beyond melanoma are reviewed. Melanin-targeted imaging holds potential value in the diagnosis, staging, and prognostic assessment of melanoma and other applications. Melanin-targeted radionuclide therapy possesses immense potential but requires more clinical validation. Furthermore, an intriguing avenue for future research involves expanding the application scope of melanin-targeted probes and exploring their value.
Topics: Humans; Melanins; Animals; Translational Research, Biomedical; Radioactive Tracers; Melanoma; Radiopharmaceuticals
PubMed: 38719238
DOI: 10.2967/jnumed.123.266945