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 α-synuclein and to the development of abnormal α-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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.