Brain iron pathways and their relevance to Parkinson's disease.
A central role of iron in the pathogenesis of Parkinson's disease (PD), due to its increase in substantia nigra pars compacta dopaminergic neurons and reactive microglia and its capacity to enhance production of toxic reactive oxygen radicals, has been discussed for many years. Recent transcranial ultrasound findings and the observation of the ability of iron to induce aggregation and toxicity of alpha-synuclein have reinforced the critical role of iron in the pathogenesis of nigrostriatal injury. Presently the mechanisms involved in the disturbances of iron metabolism in PD remain obscure. In this review we summarize evidence from recent studies suggesting disturbances of iron metabolism in PD at possibly different levels including iron uptake, storage, intracellular metabolism, release and post-transcriptional control. Moreover we outline that the interaction of iron with other molecules, especially alpha-synuclein, may contribute to the process of neurodegeneration. Because many neurodegenerative diseases show increased accumulation of iron at the site of neurodegeneration, it is believed that maintenance of cellular iron homeostasis is crucial for the viability of neurons.
Berg
D
D
Department of Neurology, Bayerische Julius-Maximilians-Universität Würzburg, Germany. daniela.berg@mail.uni-wuerzburg.de
Gerlach
M
M
Youdim
M B
MB
Double
K L
KL
Zecca
L
L
Riederer
P
P
Becker
G
G
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology*; D011499:Protein Processing, Post-Translational; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D007501:Iron