Structural characteristics of human substantia nigra neuromelanin and synthetic dopamine melanins.
Neuromelanin (NM) is a complex polymer pigment found primarily in the dopaminergic neurons of the human substantia nigra. The structure of NM is only partially characterized, and its synthesis pathway remains unknown. We used nuclear magnetic and infrared spectroscopy to examine the structure of human NM isolated from the substantia nigra compared with synthetic dopamine melanins. Biochemical analyses were used to investigate proteinaceous and dopaminergic components in these samples. Following acid hydrolysis of NM samples, small amounts of DOPA, dopamine, and a variety of amino acids were measured. These findings suggest a peptide component in NM structure. NM also appears to contain a variety of unidentified structural components possibly derived from the oxidation of dopamine. Human NM differs structurally from synthetic dopamine melanin, but both human and synthetic NM include an aromatic backbone. It is interesting that both human NM and synthetic melanin also contain a large proportion of aliphatic structures. Our results suggest that NM is a more complex pigment than synthetic dopamine melanin formed via dopamine autoxidation alone.
Double
K L
KL
Prince of Wales Medical Research Institute, Sydney, New South Wales, Australia. K.Double@unsw.edu.au
Zecca
L
L
Costi
P
P
Mauer
M
M
Griesinger
C
C
Ito
S
S
Ben-Shachar
D
D
Bringmann
G
G
Fariello
R G
RG
Riederer
P
P
Gerlach
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000032:analysis; D004295:Dihydroxyphenylalanine / Q000032:analysis; D004298:Dopamine / Q000737:chemistry*; D005858:Germany; D006801:Humans; D006868:Hydrolysis; D007558:Italy; D009682:Magnetic Resonance Spectroscopy; D008543:Melanins / Q000737:chemistry*; D008875:Middle Aged; D015394:Molecular Structure; D013378:Substantia Nigra / Q000737:chemistry*
D000596:Amino Acids; D008543:Melanins; C014121:neuromelanin; D004295:Dihydroxyphenylalanine; D004298:Dopamine