+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic neurodegeneration underlying Parkinson's disease

Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic neurodegeneration underlying Parkinson's disease

Neurotoxicity Research 5(1-2): 35-44

Neuromelanin (NM) is a granular, dark brown pigment produced in some but not all of the dopaminergic neurons of the human substantia nigra (SN). In Parkinson's disease (PD) the pigmented dopaminergic neurons of the SN degenerate, suggesting that this process is related to the presence of NM. As yet it is unknown whether NM in the parkinsonian brain differs from that found in healthy tissue and thus may fulfil a different role within this tissue. The function of NM within the pigmented neurons is unknown but other melanins are believed to play a protective role via attenuation of free radical damage. Experimental evidence suggests that NM may also exhibit this characteristic, possibly by direct inactivation of free radical species or via its ability to chelate transition metals, such as iron. NM has the ability to bind a variety of metals, seven per cent of isolated NM is reported to consist of Fe, Cu, Zn and Cr. Iron is of particular interest as this metal is highly concentrated within the SN. Up to 20 per cent of the total iron contained in the SN from normal subjects is bound within NM. Further, it was demonstrated that NM contains a protein component and that iron is bound to NM in the ferric form. Increased tissue iron found in the parkinsonian SN may saturate iron-chelating sites on NM, and a looser association between iron and NM may result in an increased, rather than decreased, production of free radical species. It is hypothesized that this redox-active iron could be released and involved in a Fenton-like reaction leading to an increased production of oxidative radicals. The resultant radical-mediated cytotoxicity may contribute to cellular damage observed in PD.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 049673993

Download citation: RISBibTeXText

PMID: 12832223

DOI: 10.1007/bf03033371

Related references

S21 Neuromelanin And Its Interaction With Iron As A Potential Risk Factor For Dopaminergic Neurodegeneration Underlying Parkinson??S Disease. Behavioural Pharmacology 17(5-6): 541, 2006

Neuromelanin-bound ferric iron as an experimental model of dopaminergic neurodegeneration in Parkinson's disease. Parkinsonism and Related Disorders 14(Suppl. 2): S185-S188, 2008

Excessive iron accumulation in the brain: A possible potential risk of neurodegeneration in Parkinson's disease. Journal of Neural Transmission 104(6-7): 649-660, 1997

Role of iron and iron chelation in dopaminergic-induced neurodegeneration: implication for Parkinson's disease. Annals of Neurology 32 Suppl: S105-S110, 1992

The pivotal role of iron in NF-kappa B activation and nigrostriatal dopaminergic neurodegeneration. Prospects for neuroprotection in Parkinson's disease with iron chelators. Annals of the new York Academy of Sciences 890: 7, 1999

Oxidative stress and mitochondrial dysfunction are the underlying events of dopaminergic neurodegeneration in homocysteine rat model of Parkinson's disease. Neurochemistry International 101: 48-55, 2016

L-3,4-dihydroxyphenylalanine (l-DOPA) modulates brain iron, dopaminergic neurodegeneration and motor dysfunction in iron overload and mutant alpha-synuclein mouse models of Parkinson's disease. Journal of Neurochemistry 150(1): 88, 2019

Long-Term Intravitreal Ranibizumab as a Potential Additional Risk Factor for Neurodegeneration in Parkinson's Disease: A Case Report. Frontiers in Pharmacology 9: 608, 2018

Microsomal prostaglandin E synthase-1 is a critical factor in dopaminergic neurodegeneration in Parkinson's disease. Neurobiology of Disease 124: 81-92, 2019

Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and MitoPark transgenic mouse models of Parkinson's Disease. Journal of Neurochemistry 141(5): 766-782, 2017

Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease. Frontiers in Aging Neuroscience 8: 196, 2016

Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson`s disease. Journal of Neurochemistry 114(6): 1687-1700, 2010

Human neuromelanin induces neuroinflammation and neurodegeneration in the rat substantia nigra: implications for Parkinson's disease. Acta Neuropathologica 116(1): 47-55, 2008

Transforming growth factor β1-mediated anti-inflammation slows progression of midbrain dopaminergic neurodegeneration in Parkinson's disease?. Neural Regeneration Research 10(10): 1578-1580, 2015

Chronic expression of H-ferritin in dopaminergic midbrain neurons results in an age-related expansion of the labile iron pool and subsequent neurodegeneration: implications for Parkinson's disease. Brain Research 1297: 17-22, 2009