In humans, melanin is the primary determinant of skin color. It is also found in hair, the pigmented tissue underlying the iris of the eye, and the stria vascularis of the inner ear. In the brain, tissues with melanin include the medulla and zona reticularis of the adrenal gland, and pigment-bearing neurons within areas of the brainstem, such as the locus coeruleus and the substantia nigra.
The melanin in the skin is produced by melanocytes, which are found in the basal layer of the epidermis. Although, in general, human beings possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and ethnic groups more frequently or less frequently express the melanin-producing genes, thereby conferring a greater or lesser concentration of skin melanin. Some individual animals and humans have very little or no melanin in their bodies, a condition known as albinism.
Because melanin is an aggregate of smaller component molecules, there are many different types of melanin with differing proportions and bonding patterns of these component molecules. Both pheomelanin and eumelanin are found in human skin and hair, but eumelanin is the most abundant melanin in humans, as well as the form most likely to be deficient in albinism.
Melanin is brown, non-refractile, and finely granular with individual granules having a diameter of less than 800 nanometers. This differentiates melanin from common blood breakdown pigments, which are larger, chunky, and refractile, and range in color from green to yellow or red-brown. In heavily pigmented lesions, dense aggregates of melanin can obscure histologic detail. A dilute solution of potassium permanganate is an effective melanin bleach.
Eumelanin polymers have long been thought to comprise numerous cross-linked 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) polymers. However, recent research into the electrical properties of eumelanin has indicated that it may consist of more basic oligomers adhering to one another by some other mechanism. Eumelanin is found in hair, areola, and skin, and the hair colors grey, black, yellow, and brown. In humans, it is more abundant in people with dark skin.
There are two different types of eumelanin. The two types are black eumelanin and brown eumelanin, with black melanin being darker than brown. Black eumelanin is mostly in non-Europeans and aged Europeans, while brown eumelanin is in mostly young Europeans.
A small amount of black eumelanin in the absence of other pigments causes grey hair. A small amount of brown eumelanin in the absence of other pigments causes yellow (blond) color hair.
Pheomelanin is also found in hair and skin and is both in lighter-skinned humans and darker-skinned humans. Pheomelanin imparts a pink to red hue and, thus, is found in particularly large quantities in red hair. Pheomelanin also may become carcinogenic when exposed to the ultraviolet rays of the sun. In chemical terms, pheomelanin differs from eumelanin in that its oligomer structure incorporates benzothiazine and benzothiazole units that are produced, instead of DHI and DHICA, when the amino acid L-cysteine is present.
Neuromelanin is the dark pigment present in pigment-bearing neurons of four deep brain nuclei: the substantia nigra (from the Latin ''black substance'') - Pars Compacta part, the locus coeruleus (''blue spot''), the dorsal motor nucleus of the vagus nerve (cranial nerve X), and the median raphe nucleus of the pons. Both the substantia nigra and locus coeruleus can be easily identified grossly at the time of autopsy because of their dark pigmentation. In humans, these nuclei are not pigmented at the time of birth, but develop pigmentation during maturation to adulthood.
Although the functional nature of neuromelanin is unknown in the brain, the pigment is made from oxyradical metabolites of monoamine neurotransmitters including dopamine and norepinephrine. Luigi Zecca and David Sulzer demonstrated that neuromelanin pigment is an autophagy product that accumulates in lysosomes, which are unable to effectively degrade it. In this way, the synthesis of neuromelanin, is protective as its encapsulation within the autophagic organelle removes it from reacting with sites in the neuronal cytosol that could lead to neurotoxicity.
While neuromelanin becomes higher throughout life in most people, the loss of pigmented neurons from specific nuclei is seen in a variety of neurodegenerative diseases. In Parkinson's disease there is massive loss of dopamine-producing pigmented neurons in the substantia nigra. High levels of neuromelanin are also detected in other primates, and in carnivores such as cats and dogs.
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