Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(8), С. 4176 - 4176

Опубликована: Апрель 10, 2022

Parkinson’s disease (PD) is an aging-related and the second most common neurodegenerative after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency neurotransmitter dopamine (DA) in striatum due to cell death nigrostriatal DA neurons. Two histopathological hallmarks exist PD: cytosolic inclusion bodies termed Lewy that mainly consist α-synuclein protein, oligomers which produced by misfolding regarded be neurotoxic, causing death; black pigments neuromelanin (NM) contained neurons markedly decrease PD. synthesis human NM similar melanin melanocytes; skin via DOPAquinone (DQ) tyrosinase, whereas DAquinone (DAQ) tyrosine hydroxylase (TH) aromatic L-amino acid decarboxylase (AADC). cytoplasm highly reactive assumed oxidized spontaneously or unidentified tyrosinase DAQ then, synthesized NM. Intracellular accumulation above a specific threshold has been reported associated neuron phenotypes. This review reports recent progress biosynthesis pathophysiology

Язык: Английский

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Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Cancers, Год журнала: 2024, Номер 16(12), С. 2262 - 2262

Опубликована: Июнь 18, 2024

Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and high mortality rate. This review discusses etiologic risk factors for melanoma, diagnostic prognostic tools, including recent advances in molecular biology, omics, bioinformatics, provides an overview its therapy. Since the incidence melanoma rising remains unacceptably high, we discuss inherent properties, melanogenesis, that make this disease resilient treatment propose use AI solve above complex multidimensional problems. We provide on vitamin D anticancerogenic report field can solutions prevention and/or therapy melanoma. Experimental papers clinicopathological studies role status signaling pathways initiated active metabolites prognosis are reviewed. conclude signaling, defined specific nuclear receptors selective activation hydroxyderivatives, benefit new or existing therapeutic approaches. target with computational biology tools solution problem.

Язык: Английский

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The role of tyrosine hydroxylase as a key player in neuromelanin synthesis and the association of neuromelanin with Parkinson’s disease

Journal of Neural Transmission, Год журнала: 2023, Номер 130(5), С. 611 - 625

Опубликована: Март 20, 2023

Abstract The dark pigment neuromelanin (NM) is abundant in cell bodies of dopamine (DA) neurons the substantia nigra (SN) and norepinephrine (NE) locus coeruleus (LC) human brain. During progression Parkinson’s disease (PD), together with degeneration respective catecholamine (CA) neurons, NM levels SN LC markedly decrease. However, questions remain among others on how associated PD it synthesized. biosynthesis pathway brain has been controversial because presence tyrosinase CA elusive. We propose following synthesis these neurons: (1) Tyrosine converted by tyrosine hydroxylase (TH) to L-3,4-dihydroxyphenylalanine (L-DOPA), which aromatic L-amino acid decarboxylase DA, β-hydroxylase NE; (2) DA or NE autoxidized quinone (DAQ) (NEQ); (3) DAQ NEQ eumelanic (euNM) pheomelanic (pheoNM) absence cysteine, respectively. This process involves proteins as cysteine source iron. also discuss whether amounts per neuromelanin-positive (NM + ) neuron are higher brain, quantitatively correlates neurodegeneration, an active lifestyle may reduce formation.

Язык: Английский

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Recent Advances in Characterization of Melanin Pigments in Biological Samples

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 8305 - 8305

Опубликована: Май 5, 2023

The melanin pigments eumelanin (EM) and pheomelanin (PM), which are dark brown to black yellow reddish-brown, respectively, widely found among vertebrates. They produced in melanocytes the epidermis, hair follicles, choroid, iris, inner ear, other tissues. diversity of colors animals is mainly caused by quantity quality their melanin, such as ratios EM versus PM. We have developed micro-analytical methods simultaneously measure PM used these study biochemical genetic fundamentals pigmentation. photoreactivity has become a major focus research because postulated relevance for risk UVA-induced melanoma. Our application many clinical studies on conditions associated with alterations Recently, besides chemical degradative methods, been characterization also discussed here.

Язык: Английский

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Promising Functions of Novel Vitamin D Derivatives as Cosmetics: A New Fountain of Youth in Skin Aging and Skin Protection

Cosmetics, Год журнала: 2024, Номер 11(2), С. 37 - 37

Опубликована: Март 1, 2024

Vitamin D is a natural photoproduct that has many beneficial effects on different organs, including skin. Active forms of vitamin and its derivatives exert biological skin cells, thus maintaining homeostasis. In keratinocytes, they inhibit proliferation stimulate differentiation, have anti-inflammatory properties, act as antioxidants, DNA damage repair after ultraviolet (UV) exposure. melanocytes, also cell proliferation, apoptosis antioxidants. fibroblasts, affect fibrotic processes collagen production, promote wound healing regeneration. On the other hand, cells ability to activate directly. These activities, along with projected topical application derivatives, are promising for care photo protection can be used in prevention or possible reversal aging.

Язык: Английский

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The Dark Side of Melanin Secretion in Cutaneous Melanoma Aggressiveness

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Май 10, 2022

Skin cancers are among the most common worldwide and increasingly prevalent. Cutaneous melanoma (CM) is characterized by malignant transformation of melanocytes in epidermis. Although CM shows lower incidence than other skin cancers, it aggressive responsible for vast majority cancer-related deaths. Indeed, 75% patients present with invasive or metastatic tumors, even after surgical excision. In CM, photoprotective pigment melanin, which produced melanocytes, plays a central role pathology disease. Melanin absorbs ultraviolet radiation scavenges reactive oxygen/nitrogen species (ROS/RNS) resulting from exposure. However, scavenged ROS/RNS modify melanin lead to induction signature DNA damage cells, namely cyclobutane pyrimidine dimers, known promote immortalization carcinogenesis. Despite triggering promoting initial tumor growth, presence inside cells described negatively regulate their invasiveness increasing cell stiffness reducing elasticity. Emerging evidence also indicates that secreted required immunomodulation microenvironment. transforms dermal fibroblasts cancer-associated fibroblasts, suppresses immune system promotes angiogenesis, thus sustaining progression metastasis. Here, we review current knowledge on secretion aggressiveness molecular machinery involved, as well impact microenvironment responses. A better understanding this players involved could enable modulation become therapeutic strategy impair invasion metastasis and, hence, reduce burden CM-associated

Язык: Английский

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The small molecule ML233 is a direct inhibitor of tyrosinase function

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Март 28, 2025

Melanogenesis is the biological process regulating synthesis of melanin pigments in melanocytes. Defective melanogenesis associated with numerous human skin diseases, including, but not limited to, albinism, vitiligo, melasma, and hypo- hyperpigmentation disorders. Tyrosinase rate-limiting enzyme controlling melanogenesis, hence tremendous efforts have been made to identify potent safe inhibitors tyrosinase function. However, despite decades research, currently there no effective treatment that inhibits or activity adverse side effects. In this study, we report characterization ML233 chemical as a inhibitor vivo vitro. We demonstrate reduces production zebrafish model observable significant toxic effects, murine melanoma cells. also predict these effects are mediated through direct tyrosinase-ML233 interaction, i.e., binding molecule active site protein inhibit its Together, our results reveal plays roles both healthy pathological cells via inhibition production. ML233-mediated potentially approach alleviate symptoms melanocyte-associated diseases thereby substantially improve health.

Язык: Английский

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Interaction of Melanin with Metal Ions Modulates Their Cytotoxic Potential

Applied Magnetic Resonance, Год журнала: 2021, Номер 53(1), С. 105 - 121

Опубликована: Июль 12, 2021

Abstract Melanin is one the most common biological pigments. In humans, specialized cells called melanocytes synthesize pigment from tyrosine and 3,4-dihydroxyphenylalanine via enzyme-catalyzed reactions spontaneous processes. The formed melanin granule consists of nanoaggregates oligomers containing different monomers. Although main function protection against damage solar radiation, may also be involved in oxidative stress. latter function, sequestration redox-active metal ions scavenging reactive oxygen species are importance. paper reviews basic physicochemical properties responsible for binding discusses specific conditions that induce cytotoxicity such as iron copper by facilitating their redox activation release melanin. While value EPR spectroscopy other EPR-related techniques study emphasized, concomitant use methods efficient approach.

Язык: Английский

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Zebrafish in dermatology: a comprehensive review of their role in investigating abnormal skin pigmentation mechanisms

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 23, 2023

Skin pigmentation abnormalities, ranging from aesthetic concerns to severe hyperpigmentation disease, have profound implications for individuals’ psychological and economic wellbeing. The intricate etiology of our evolving comprehension its underlying mechanisms underscore the need robust animal models. Zebrafish, renowned their transparent embryos genetic parallels humans, been spotlighted as a pivotal model skin studies. This review offers concise overview zebrafish attributes, highlighting shared melanin production pathways with humans. We systematically dissect diverse strategies craft models abnormal pigmentation, spanning physical, chemical, interventions, while critically appraising merits constraints each approach. Additionally, we elucidate metrics employed gauge efficacy these Concluding, cast visionary gaze on prospective breakthroughs in domain, aiming steer forthcoming efforts refined research.

Язык: Английский

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Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase

Опубликована: Март 21, 2022

Parkinson’s disease (PD) is an aging-related and the second most common neurodegenerative after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency neurotransmitter dopamine (DA) in striatum due to cell death nigro-striatal DA neurons. Two histopathological hallmarks exist PD: cytosolic inclusion bodies termed Lewy that mainly consist α-synuclein protein, oligomers which produced by misfolding regarded be neurotoxic, causing death; black pigments neuromelanin (NM) contained neurons markedly decrease PD. Synthesis human NM similar melanin melanocytes; Melanin synthesis skin via DOPAquinone (DQ) tyrosinase, whereas DAquinone (DAQ) tyrosine hydroxylase (TH) aromatic L-amino acid decarboxylase (AADC). cytoplasm highly reactive assumed oxidized spontaneously or unidentified tyrosinase DAQ then synthesized NM. Intracellular accumulation above a specific threshold was reported associated neuron phenotypes. This review reports recent progress biosynthesis pathophysiology

Язык: Английский

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