title: Neuromelanin-bound ferric iron as an experimental model of dopaminergic neurodegeneration in Parkinson's disease.
abstract: This article briefly reviews findings from studies on neuromelanin (NM)-bound ferric iron, which provide unique insights into the physiological functions of NM and possible pathophysiological mechanisms underlying dopaminergic neuronal cell death in Parkinson's disease (PD). NM is considered an endogenous iron-binding molecule of pigmented neurons and is believed to play a physiological role in intraneuronal iron homeostasis. In PD, where nigral iron levels are increased, saturation of high-affinity iron-binding sites on NM may overwhelm the protective capacity of this molecule, leading instead to an increase in redox-active iron, and subsequent cellular damage both in vitro and in vivo. Available data also suggest that the iron released from NM affects the ubiquitin-proteasome system in mitochondria, leading to the failure to clear proteins such as alpha-synuclein and to the development of abnormal alpha-synuclein-immunopositive Lewy bodies that contribute to dopaminergic nerve cell death in PD. NM-bound ferric iron mimics certain characteristic features of the human disease in vitro and in vivo (face validity), in conformity with the theoretical rationale for PD (construct validity) and predicts aspects of PD behaviour and neurobiology (predictive validity) that makes it a valid experimental model with which to study the mechanisms of dopaminergic neurodegeneration in PD.
authors.affiliation: University of Würzburg, Department of Child and Adolescent Psychiatry and Psychotherapy, Laboratory for Clinical Neurobiology, Würzburg, Germany. manfred.gerlach@uni-wuerzburg.de
authors.forename: Manfred
authors.initials: M
authors.lastname: Gerlach
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
authors.forename: Kay L
authors.initials: KL
authors.lastname: Double
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism*; D009410:Nerve Degeneration / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology
chemical_list: D008543:Melanins; C014121:neuromelanin; D007501:Iron