Link 15- Neuromelanin
www.tightrope.it/nicolaus/index.htm
At present little is definitely
known about the structure of
neuromelanin : Even the elemental composition is uncertain. This
is largely due to the relative inaccessibility of the pigment
and the difficulties connected with liberating the granules
from the surrounding lipid matrix in which they are deeply embedded
In early studies
a complex
purification procedure was
used involving
prolonged proteolytic digestion
with trypsin or pronase, treatment with lysing solutions, extensive extracions
with organic solvents, and
in some cases
drastic acid hydrolysis Spectroscopic studies of the pigment
preparations thus obtained did not provide
evidence for any distinguishing
structural feature except a
vague similarity of the absorption
spectrum to
that of dopamine melanin
An improved procedure for isolating human
neuromelanin has been developed This
involves extraction of lipids and
proteins with 2% sodium cholate in 30% ethanol followed
by 2% SDS in 10% glycerol.
Reductive hydrolysis of the pigment thus obtained
with idroiodic acid and real phosphorous yilded
4-amino-3-hydroxyphenylethylamine in large quantities along with trace amounts
of 4-amino-3-hydroxyphenylalanine indicating that 5-cysdopamine and 5-cysdopa,to
a lesser extent,both concur to form the black material. Dopamine and small
quantities of dopa were also obtained by hydrolysis,whereas permanganate
oxidation afforded some 2,4,5,-pyrroletricarboxylic acid (PTCA).These
data suggest a mixed type
melanin derived from dopamine in which pheomelanic and eumelanic type components
coexist, probably as a
result of an exhaustion of
the GSH- cysteine
defense system
of the substantia
nigra neurons.
Other researcher failed to
detect cysdopamine- derived units in
human substantia nigra melanin. On the other hand, it is
reported analytical and spectroscopic
data suggesting that 5
cysdopa or 5-cysdopamine linked to a palmityl residue are the most abundant constituents
of human neuromelanin
Although the role of neuromelanin is not known
studies of the physicochemical properties of the pigment have given rise to
several hypotheses that may or not mutually related . A gallery of relevant
papers are listed below :
------------------------------------------------------------------
M.E.Lacy Neuromelanin
: A hypothetical component of bioelectronic mechanism in brain function
Physiol.Chem. Phys.
15, 319-324, 1981
------------------------------------------------------------------------
M.B.H.
Youdim, D.Ben-Shachar, P.Riederer Is
Parkinson disease a progressive
siderosis of substantia nigra in
iron and melanin-induced neurodegeneration
?
Acta Neurol.Scand., 126, 47-54,
1989 .
--------------------------------------------------------------
J.M.Rabey, F.
Hefti Neuromelanin synthesis
in rat and human substantia
nigra
J.Neural. Transm . 2, 1-14, 1990 ) .
----------------------------------------------------------------
One view is that neuromelanin could function as
a device for the inactivation of harmfully excited molecules into innocuous
vibrational energy
( J., McGinness,
P. Proctor, The
importance of the fact that melanin is black
J. Theor. Biol. 39, 677-578, 1973 ;
J.McGinness, P.Corry, P.Proctor
Amorphous semiconductors switching in melanins Science 183,
853-854, 1974 )
. www.organicsemiconductors.com
----------------------------------------------------------------------
Other authors have postulated that neuromelanin
could exert a protective role by acting as a sink for free radicals
( B.Commoner
, J.Townsend, J.E.Pake Free
radicals in biological material
Nature, 174, 689-691, 1954
) or as a redox buffer against reducing or oxidizing toxic conditions (
E.V.Gan, K.M. Lam, H.F.Haberman, I. A. Menon, Electron
transfer properties of melanin
Br.J.Dermatol,
96, 25-28, 1977
; Arch.Biochem.Biophys., 173, 666-672, 1976 ) .
-----------------------------------------------------------------
Another property of neuromelanin which is
typical of eumelanins is the ability to bind a number of foreign substances and
to retain them for a very long time
( R.M.J.Ings
The melanin binding of drugs and its implications
Drug
Metabol. Rev. 15, 1185-1212, 1984)
).
---------------------------------------------------------------------
( N.G.Lindquist,
B.S.Larsson, A.Lyden-Sokolowski Neuromelanin and its
possible protective and destructive properties
Pigment Cell Res. 1, 133-136, 1987
)
This has led to suggest that neuromelanin may
protect the surrounding cells by keeping potentially harmful substances bound
and thereafter slowly releasing them in low, non-toxic concentrations.
------------------------------------------------------------------
( F.M. Forrest Evolutionary origin extrapyramidal disorders in drug
treated mental patients ,its significance, and the role of neuromelanin
Adv.Biochem.Psychopharmacol., 9, 255-268,
1974 )
An
interesting theory envisages neuromelanin as serving a
biocybernetic function whereby its lack or depletion causes the substantia nigra
to revert from its neuroendocrine role to its original motoric role. Moreover it
would inhibit the bioelectric activity of the neuron producing a decrease in the
cell s discharge frequency by controlling the electron flow from the cell
cytoplasm into the original axon cylinder.
-----------------------------------------------------------
Polyindoles obtained from anodic coupling of
indoles are electroconductive materials and display a noticeable interest since
they have been considered in applications such as sensors and because they may
be model polymers for biopolymers such as melanins.
(
A.Berlin, A.Canavesi, G.Schiavon,
S.Zecchin, G.Zotti Electrooxidation products of methylindoles
: Mechanisms and structures
Tetrahedron 52,
7947-7960, 1996
)
---------------------------------------------------------
The pigmented neurons of substantia nigra
are typically lost in Parkinsons diseases : however the possible relationship
between neuronal
vulnerability and the presence of neuromelanin has not been elucidated.
( L.Zecca, F.A.Zucca,
P.Costi,D.Tampellini, A.Gatti, M.Gerlach, P.Riederer, R.G.Fariello, S.Ito,
M.Gallorini, D.Sulzer.
The neuromelanin of
human substantia nigra : structure,
synthesis, and molecular behaviour
J.Neural.Transm. Suppl, (65), 145-155, 2003 )
---------------------------------------------------
------------------------------------------------------------------------
The hydrate form and possible neuromelanin
precursors :
Units or precursors
SALSOLINOL black (brown)
PHEOMELANIN (brown)
R = H ;R1
= H ; R2 = CH2
CH (NH2) ( COOH)
Tryptophane- black
R = H ; R1
= COOH ; R2 = H
DHICA-black
(brown)
R = H ; R1
= 2H ; R2 = 2H
Dopamine -black
R = H ; R1 = H ; R2
= CH2 CH2N
( CH3 )2
Bufotenin -black
-----------------------------------------------------------
For adrenalin-black a tetrameric units is showed. Pyrrolidine ring may be
present (J. Harley-Mason,
The Chemistry of Adrenochrome and its derivatives
Soc. 1276, 1950
)
Nero
di Adrenalina
Found C% 54.7 H% 4.9 N% 7.0
Calculated for C9 H9 O4 N
: C% 55.4 H% 4.6 N%
7.2
The
Proctor McGinness effect ( www.organicsemiconductors.com ) of neuromelanin has not been taken into consideration.