Biological Role of Neuromelanin in the Human Brain and Its Importance in Parkinson's Disease

Double, Kay L.; Maruyama, Wakako; M, Naoi; Gerlach, Manfred; Riederer, Peter

doi:10.1002/9783527636150.ch8

Cited by 6 publications

(5 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NM predominates in catecholaminergic neurons of the SN and the locus coeruleus and differs from peripheral melanins produced in the hair, skin, and eyes (Bogerts, ; Double et al., ; Saper and Petito, ; Zecca et al., ). It was suggested that NM is formed by the oxidation of catecholamines (Bogerts, ; Fedorow et al., ; Graham, ; Mann and Yates, ; Napolitano et al., ).…”

Section: Discussionmentioning

confidence: 99%

Biosynthetic pathway to neuromelanin and its aging process

Wakamatsu

Murase

Zucca

et al. 2012

Pigment Cell Melanoma Res

View full text Add to dashboard Cite

Subscribe to PCMR and stay up-to-date with the only journal committed to publishing basic research in melanoma and pigment cell biology As a member of the IFPCS or the SMR you automatically get online access to PCMR. Sign up as a member today at www.ifpcs.org or at www.societymelanomaresarch.org were used as markers of benzothiazine and benzothiazole units, respectively. By following the time course of the biosynthetic pathway of synthetic NM, we found that neurotoxic molecules are trapped in NM. An aging simulation of synthetic NM showed that benzothiazine units in NM are gradually converted to benzothiazole during the aging process. Thus, natural NM was found to be similar to aged (heated) NM prepared from a 2:1 molar ratio of DA and Cys.

show abstract

Section: Discussionmentioning

confidence: 99%

Biosynthetic pathway to neuromelanin and its aging process

Wakamatsu

Murase

Zucca

et al. 2012

Pigment Cell Melanoma Res

View full text Add to dashboard Cite

show abstract

“…In conclusion, NM is an enigmatic pigment, but it is irrefutably not an inert waste product of neuronal metabolism, as previously believed [ 49 ]. In fact, NM accumulation takes place over the entire life span of an organism, and the NM pigments appear to contain the story of one’s life exposure to several endogenous and environmental metals [ 1 ].…”

Section: Discussionmentioning

confidence: 62%

Toothed Whales Have Black Neurons in the Blue Spot

Sacchini

Fernandez

Mompeó

et al. 2022

Veterinary Sciences

View full text Add to dashboard Cite

Neuromelanin (NM) is a dark polymer pigment that is located mostly in the human substantia nigra, and in the locus ceruleus, referred to as “the blue spot”. NM increases linearly with age, and has been described mainly in the human brain; however, it also occurs in the neurons of monkeys, horses, giraffes, cattle, sheep, goats, dogs, rats, and even in frogs. While in most of these mammals NM shows the histochemical and ultrastructural features typical of lipofuscins, human NM is confined within cytoplasmic organelles that are surrounded by a double membrane, suggesting an autophagic origin. In a study on the morphology of the locus ceruleus of the family Delphinidae, the presence of a variable quantity of NM in the interior of locus ceruleus neurons was observed for the first time; meanwhile, nothing is known about its ultrastructure and composition. Transmission electron microscopy demonstrated in two toothed whales—an Atlantic spotted dolphin (Stenella frontalis; family Delphinidae) and a Blainville’s beaked whale (Mesoplodon densirostris; family Ziphiidae)—the presence of melanin granules associated with lipid droplets and membranes that were very similar to that of human NM. The relationship between NM and neuronal vulnerability must be studied in depth, and cetaceans may offer a new natural-spontaneous comparative model for the study of NM and its implication in neurodegenerative diseases.

show abstract

“…In light of our findings, it would be informative to examine the role of KLF6 inactivation in melanoma initiation and how the extracellular matrix could modulate this process. Furthermore, these and other hits from our screen merit further exploration in the context of other diseases, because aberrant melanin production is associated not only with skin pigmentation disorders but also with Parkinson’s disease and auditory disorders, which have been linked to loss of neuromelanin in substantia nigra and cochlear melanin in the inner ear, respectively ( 62 , 63 ). Furthermore, select loci identified in our screen show association with skin color variation and evidence of recent adaptations in human populations.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide genetic screen uncovers determinants of human pigmentation

Bajpai

Swigut

Mohammed

et al. 2023

Science

View full text Add to dashboard Cite

Skin color, one of the most diverse human traits, is determined by the quantity, type, and distribution of melanin. In this study, we leveraged the light-scattering properties of melanin to conduct a genome-wide screen for regulators of melanogenesis. We identified 169 functionally diverse genes that converge on melanosome biogenesis, endosomal transport, and gene regulation, of which 135 represented previously unknown associations with pigmentation. In agreement with their melanin-promoting function, the majority of screen hits were up-regulated in melanocytes from darkly pigmented individuals. We further unraveled functions of KLF6 as a transcription factor that regulates melanosome maturation and pigmentation in vivo, and of the endosomal trafficking protein COMMD3 in modulating melanosomal pH. Our study reveals a plethora of melanin-promoting genes, with broad implications for human variation, cell biology, and medicine.

show abstract

Biological Role of Neuromelanin in the Human Brain and Its Importance in Parkinson's Disease

Cited by 6 publications

References 84 publications

Biosynthetic pathway to neuromelanin and its aging process

Biosynthetic pathway to neuromelanin and its aging process

Toothed Whales Have Black Neurons in the Blue Spot

A genome-wide genetic screen uncovers determinants of human pigmentation

Contact Info

Product

Resources

About