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Topic: Neuromelanin

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	Synthetic Inorganic Model Complexes of Iron Neuromelanin (Site not responding. Last check: 2007-10-11)
		Duke University, Durham, NC Neuromelanin is an insoluble biopolymer derived from the oxidation of dopamine and cysteinyldopamine.
		Studies have shown that neuromelanin selectively deteriorates during the onset of Parkinson 's disease.
		However, the limited availability of neuromelanin, the difficulty in extracting and purifying the pigment and the lack of an adequate model have resulted in an insufficient understanding of the biopolymer structure and function.
	acs.confex.com /acs/56serm/techprogram/P13116.HTM (118 words)

	PathonhysioIogy of Parkinson's disease
		Neuromelanin, in contrast to eumelanin, is not seguestered within membrane bound organelles and has a high affinity for potentially toxic nucleophiles, including those toxins implicated in the aetiology of Parkinson's disease.
		Th vivo deposition of mature neuromelanin is seen from the age of 6 months, increasing with aging up to 60 years after wich there is a decrease, a decrease which is accelerated in Parkinson's disease with preferential loss of the heavily pigmented cells.
		Although deposition of neuromelanin is not seen microscopically until after the age ot 6 months, it is probable that dopamine oxidation, itself a free radical generating reaction, is an ongoing process.
	sabryabdelfattah.tripod.com /docs/PATHPARK.htm (662 words)

	Discussion (Site not responding. Last check: 2007-10-11)
		The accumulation of neuromelanin with ageing would be responsible for the pigmented neurons degeneration in older people and perhaps in some individuals (Parkinson's disease affected); the accumulation of this substance may result in the decrease of ribosomal RNA content and finally into nucleolar lesions (23).
		Neuromelanin is compartmentalized in granules showing tripartite and globular structure consisting of vesicular bodies protruding from a granular or linear lattice (18).
		The present neuromelanin age appears to be more fruitful of studies about the implication of radical species, such as active oxygen, electrophilic species scavengers such as GSH or cysteine and about the enzymes involved in these scavenging processes such as SOD (superoxide dismutase), catalase, peroxidases, glutathione-S-transferase, glutathione reductase ecc.
	www.ulb.ac.be /medecine/loce/espcr/b_iss/Dis-18a.htm (1414 words)

	Melanin - Wikipedia, the free encyclopedia
		Neuromelanin has been detected in primates and in carnivores such as cats and dogs.
		Persons with Parkinson's disease, a disorder that affects neuromotor functioning, have been shown to have decreased neuromelanin in the substantia nigra as consequence of diminished dopamine synthesis.
		In addition to melanin deficiency, the molecular weight of the melanin polymer may be decreased due to various factors such as oxidative stress, exposure to light, perturbation in its association with melanosomal matrix proteins, changes in pH or in local concentrations of metal ions.
	en.wikipedia.org /wiki/Melanin (2676 words)

	Lewy Body Disease
		The acidophilic pink granule is a small eosinophilic cytoplasmic granule found in pigmented neurons, distributed among the neuromelanin granules.
		Neuromelanin debris may also be found within macrophages.
		It also appears that neurons containing neuromelanin are intrinsically more susceptible to the effects of free radical damage.
	www.seniorpsychiatry.com /pages/articles/lewy.html (3282 words)

	Riederer,P
		Using synthetic neuromelanins, we have demonstrated that Py-GC/MS is suitable for identification and differentiation of both eumelanin (dopamine-derived) and pheomelanin (cysteinyldopamine-derived) component of the pigment.
		Neuromelanin (NM) is a dark polymer pigment produced in specific populations of catecholaminergic neurons in the brain.
		Neuromelanin is a dark brown pigment present at high concentrations in dopaminergic neurones of the human substantia nigra (SN).
	lib.bioinfo.pl /auth:Riederer,P (8669 words)

	Neuropathology For Medical Students
		The pigment in the substantia nigra is dark (arrows) because of the presence of brown neuromelanin in neurons (below).
		Neuromelanin is produced in the catabolism of DOPamine, the neurohumor synthesized by these neurons.
		In addition to the presence of Lewy bodies, Parkinson's disease is characterized by degeneration of the nigral neurons, with liberation of the neuromelanin into the adjacent tissue where it is phagocytosed and carried away by macrophages.
	www.pathology.vcu.edu /WirSelfInst/neuro_medStudents/BASALGANG.html (1280 words)

	Purified human neuromelanin, synthetic dopamine melanin as a potential model pigment, and the normal human substantia ... (Site not responding. Last check: 2007-10-11)
		Neuromelanin is a poorly understood pigment that accumulates in catecholaminergic neurons during normal aging.
		Electron paramagnetic resonance spectroscopy, an especially effective technique for investigating melanins, is used in the present study to show unambiguously that neuromelanin is a melanin; however, it is not well modeled by synthetic dopamine melanin and thus is an atypical melanin.
		Combined with previous histochemical data, these observations have implications for the mechanism through which neuromelanin accumulates in vivo and are consistent with its having a cytoprotective function under normal conditions, but a cytotoxic role at advanced ages and in patients with Parkinson's disease.
	www.arclab.org /medlineupdates/abstract_8390568.html (296 words)

	Substantia nigra neuromelanin: structure, synthesis, and molecular behaviour -- Zecca et al. 54 (6): 414 -- Molecular ...
		Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles.
		Neuromelanin containing neurons of the substantia nigra accumulate iron and aluminium in Parkinson's disease: a LAMMA study.
		The roles of neuromelanin binding of metal ions, and oxidative cytotoxicity in the pathogenesis of Parkinson's disease: a hypothesis.
	mp.bmjjournals.com /cgi/content/full/54/6/414 (3100 words)

	The Parkinson Alliance (Site not responding. Last check: 2007-10-11)
		Another area of the basal ganglia, the locus ceruleus (LC), is nearly as damaged in PD brains as is the substantia nigra (SN).
		Their work will be done in tissue autopsied from healthy humans who died without neurologic or psychiatric disease and compared with tissue from known PD patients.
		Neuromelanin (NM) seems to be able to provide protection based on its ability to chelate trace metals and accumulate toxins, “flushing” them from the brain.
	www.parkinsonalliance.net /research/abstracts/neuromelanin.asp (224 words)

	www.ackee.com :: Mekwitalk - Forward Thinking - Multiculturalism, Cult Archaeology, and Pseudoscience (Site not responding. Last check: 2007-10-11)
		Neuromelanin is the compound found in the brain; eumelanin is present in the skin.
		White albinos have a normal amount of neuromelanin, and, because the amount of neuromelanin is directly proportional to age, an old albino has more neuromelanin than a fl teenager.
		Practically all of their assertions about neuromelanin are false; even if they were all true, all humans would have the same abilities, regardless of skin color.
	www.ackee.com /mekwitalk/read.php?f=7&i=4738&t=4738 (6617 words)

	Uro i benene, Urolige ben - Restless Legs-Portalen (Site not responding. Last check: 2007-10-11)
		Neuromelanin cells from the SN of four RLS and four control brains were isolated by laser capture microdissection, and a profile of iron-management protein expression was obtained by immunoblot analysis.
		Ferritin, divalent metal transporter 1, ferroportin, and transferrin receptor (TfR) were decreased in RLS neuromelanin cells compared with control.
		This protein profile in RLS neuromelanin cells is consistent with iron deficiency with the exception that TfR expression was decreased rather than increased.
	www.restlesslegs.no /jernmangel.asp?ID=52 (263 words)

	POWMRI - Biochemical changes in Parkinson's disease
		laboratory is neuromelanin, a dark-coloured pigment molecule found in significant quantities in dopamine-containing neurons in the human brain, but not in other species.
		We recently demonstrated that the lipids in neuromelanin are primarily those formed in the isoprenoid pathway, such as dolichol and cholesterol.
		The brown neuromelanin pigment has a normal appearance in the cell from a healthy brain (left panel: control), in contrast the pigment is measurably darker in colour in the brain cell from the person with Parkinson’s disease (right panel: PD).
	www.powmri.edu.au /research/pdda/pdrd/cellular/biochem_ch.htm (525 words)

	INABIS '98 - Model Neuromelanins as Antioxidative Agents During Lipid Peroxidation (Site not responding. Last check: 2007-10-11)
		In this context, neuromelanin deposition in dopaminergic neurons of the substantia nigra may be regarded as a protective mechanism against potentially cytotoxic o-quinones produced during dopamine oxidation [21,22].
		The fatty acid hydroperoxide-reducing ability demonstrated for the model neuromelanins appears to be involved in the mechanism of antioxidative activity of neuromelanin.
		2.Graham, DG (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones.
	www.mcmaster.ca /inabis98/kostrzewa/wilczok0432/two.html (3088 words)

	Paper: 414 :: (Site not responding. Last check: 2007-10-11)
		Early histological studies revealed the presence of increasing amounts of neuromelanin in the substantia nigra with aging in higher mammals, showed that the neuromelanin granules are surrounded by a membrane, and comparatively evaluated the pigmentation of the substantia nigra in diVerent animal species.
		In these later studies, neuromelanin was identified as a genuine melanin with a strong chelating ability for iron and an aYnity for compounds such as lipids, pesticides, and MPP+.
		The aYnity of neuromelanin for a variety of inorganic and organic toxins is consistent with a postulated protective function for neuromelanin.
	www.medical-papers.com /neuromelanin+substantia+nigra+iron+human (468 words)

	Evidence for specific phases in the development of human neuromelanin. (Site not responding. Last check: 2007-10-11)
		Neuromelanin is a dark-coloured pigment which forms in the dopamine neurons of the human midbrain.
		Optical density and area measurements of unstained neuromelanin in ventral substantia nigra neurons from 29 people spanning the ages of 24 weeks to 95 years old, demonstrated three developmental phases.
		Neuromelanin was not present at birth and initiation of pigmentation began at approximately 3 years of age, followed by a period of increasing pigment granule number and increasing pigment granule colouration until age 20.
	www.arclab.org /medlineupdates/abstract_15916835.html (189 words)

	FROM THE STARS TO MIND
		Based upon the present state of the art, the substantia nigra melanin is involved in movement coordination and protection of neurons against oxidative stress being moreover supposed to be instrumental to neuronal death and Parkinson’s disease; in the eye, ocular melanin is devoted to absorption of excessive light; in the ear, in deadening acoustic waves.
		In humans and primates, neuromelanin predominates in the catecholaminergic neurons of the substantia nigra and locus coeruleus, were dopamine, epinephrine and nor epinephrine are present in high concentration, raising the question, whether this melanin is composed by one pigment only, or by a mixture of two or more.
		In later studies neuromelanin was identified as a genuine melanin with a strong chelating ability for iron and affinity for several organic compounds.
	www.brunonic.org /Nicolaus/neuromelaninandbiological.htm (8397 words)

	LIEBERMAN PARKINSON CLINIC - Preventing Parkinson: Melanin (Site not responding. Last check: 2007-10-11)
		Neuromelanin is a strong chelators of metals; it accumulates iron, zinc and other metals and in dopamine neurons of substantia nigra the complex neuromelanin-Fe is the major iron deposit.
		The neuromelanin synthesis in neurons is driven by excess cytosolic catecholic derivatives which are not stored by synaptic vesicles and this may provide an antioxidant mechanism for catecholamine neurons.
		The darker neuromelanin in PD accumulates the lipoprotein alpha-synuclein.
	www.liebermanparkinsonclinic.com /content/view/540/31 (474 words)

	CNR-->Institute ITB (Site not responding. Last check: 2007-10-11)
		A linear accumulation of neuromelanin in neurons during aging and decrease in Parkinson’s disease was observed.
		In neuronal cultures it was demonstrated that neuromelanin synthesis is driven by excess cytosolic catechols which are not stored by synaptic vesicles and then providing an antioxidant mechanism inside neurons.
		On the other hand it was found that extraneuronal neuromelanin, released by dying neurons, is neurotoxic since it activates microglia with release of toxic molecules (NO, TNF and IL-6) damaging neurons.
	www.cnr.it /istituti/Descrizione_eng.html?cds=100 (3351 words)

	Congresso Società Italiana di Neurologia (SIN)
		Melanin is constituted of dopamine which, copolymerising with cyclical groups containing sulphur, forms "granules of insoluble protein pigment" (melanosomes); the neuromelanin, contained in the pigmented neurons, is melanin polymer incorporated in a glycolipid matrix.
		Since the neuromelanin is a melanin polymer we must expect that, in the neurons, the neuromelanin has a physiological role as a "deposit" of ready dopamine (for use when needed, without having to be synthesised when the need arises).
		The identity of the chemical-physical structure of the melanin and of the neuromelanin shows that the pigmented neurons of the Substantia Nigra (SN) phagocytize from outside the melanin and incorporate it into a glycolipid matrix.
	www.domenicofiore.it /sm/37-eng.htm (392 words)

	Parkinson's Unity Walk
		Project Update: In the substantia nigra of PD patients a proliferation of microglial cells surrounding neuromelanin granules was observed thus indicating a condition of chronic inflammation in PD. In this project the effect of human neuromelanin and synthetic neuromelanins will be investigated on glial culture.
		A range of neuromelanin levels, and gold particles used as inert controls, were deposited on cortical astrocytes, and microglia observed and counted over the course of one week.
		When neuromelanin is present, we observe that the microglia move towards the substance, surround it and ingest it: in fact, particles of the pigment are easily observed within these cells.
	www.unitywalk.org /na_grants2003.shtml (2994 words)

	European Iron Club: Metal Based Neurodegenerative Diseases; Section 4
		The increase in SN iron content, detectable in 90% of individuals affected by the disease by ultrasound measurements, was also detectable in 45% of relatives of Parkinson's disease patients, indicating a degree of inheritance of this disorder.
		The function of neuromelanin in the pigmented neurons is unknown but it could play a protective role via attenuation of free radical damage by binding transition metals, particularly iron.
		Whether the ability of the neurones to synthesis neuromelanin is impaired in PD patients is unknown, although it is reported that the absolute concentration of nigral neuromelanin is less than 50% in PD with respect to age matched controls.
	www.euro-iron.org /art0104.shtml (1825 words)

	The Franz Lab
		We are particularly interested in understanding the role of iron in Parkinson's disease; two targets of study in this area include the pigment neuromelanin and the protein alpha-synuclein.
		We are also interested in understanding metal ion homeostasis and trafficking, and are currently investigating the copper-binding properties of proteins involved in cellular copper uptake.
		Neuromelanin is an insoluble, fl pigment that accumulates with age in dopamine-producing neurons.
	www.chem.duke.edu /~kfranz/labgroup/Research/reseach_index.html (461 words)

	Dissertations from Karolinska Institutet - Published by Karolinska Institutet Karolinska Institutet - ki.se
		However, a decline was noted in number of tyrosine hydroxylase-immunoreactive neurons that was paralleled by an increase in neuromelanin pigmentation with advancing age.
		Striatal dopamine levels were also significantly lower in old monkeys as compared to young animals (-25% in the putamen and —20% in the caudate), suggesting that nigral neurons undergo a shift in phenotype during aging that may contribute to functional decreases in the striatum.
		The roles of aging and neuromelanin in increased vulnerability of pigmented populations of neurons and the pathological role of alpha-synuclein in PD may be all clarified by the use of MPTP in the non-human primate.
	diss.kib.ki.se /2006/91-7140-624-7 (829 words)

	INABIS '98 - The Role of Catecholamine O-quinones in Health and Disease: What We Know and What We Don't Know (Site not responding. Last check: 2007-10-11)
		Neuromelanin is not found in these cells at birth but appears at around 6 months of age and then steadily accumulates during life.
		Neuromelanin is normally neuroprotective as it chelates toxic heavy metals and has antioxidant properties (Korytowski et al.
		Enochs, W.S., Sarna, T. Zecca, L. Riley, P.A. and Swartz, H.M. (1994) The roles of neuromelanin, binding of metal ions and oxidative cytotoxicity in the pathogenesis of Parkinson’s disease: an hypothesis.
	www.mcmaster.ca /inabis98/kostrzewa/smythies0199/two.html (4395 words)

	The Biochemistry of Parkinson's Disease - Page 3 - BrainTalk Communities (Site not responding. Last check: 2007-10-11)
		Although they are attached to different proteins, the pigment part of Neuromelanin is identical to that of the pigment melanin in skin.
		However, it is difficult to see how somebody without PD would come to produce neuromelanin, because unless there was a fault in dopamine biosynthesis, particularly from L-dopa to dopamine, it could not readily occur.
		Neuromelanin is a potential symptom of PD, rather than an inevitable symptom of PD, and need not occur.....
	brain.hastypastry.net /forums/showthread.php?p=291312 (4180 words)

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