Iron in brain function and dysfunction with emphasis on Parkinson's disease.
Metals such as lead, zinc, copper, aluminum and manganese have been implicated in neuropsychiatric disorders. However, until fairly recently the role of iron in brain function was rather obscure, because little attention was paid to its metabolism in the brain. It is now apparent that maintenance of brain iron homoeostasis is important for the normal functioning of his organ. Most of the studies have been directed towards the cognitive and attentional deficit resulting from nutritional iron deficiency. Evidence so far suggests subsensitivity of striatal dopamine neurotransmission. By contrast the selective increase in free iron in the substantia nigra pars compacta of parkinsonian brains is thought to initiate oxidative stress, from iron-induced liberation of cytotoxic oxygen free radicals. Such radicals are known to promote membrane fluidity, alteration in cellular calcium homoeostasis, lipid peroxidation and finally cell death in systemic organs. Evidence supporting similar processes being responsible for nigrostriatal dopamine neuron degeneration in Parkinson's disease is now becoming available. Such possibilities afford the development of neuroprotective drugs as a means to retard the progression of this disorder. These include other selective monoamine oxidase B inhibitors, iron chelators with the ability to cross the blood-brain barrier, selective calcium channel antagonists and mitochondrial electron transport system protectors.
Youdim
M B
MB
Technion-Faculty of Medicine, Rappaport Family Research Institute, Haifa, Israel.
Ben-Shachar
D
D
Riederer
P
P
D000747:Anemia, Hypochromic / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D004298:Dopamine / Q000502:physiology; D006801:Humans; D007501:Iron / Q000502:physiology*; D010300:Parkinson Disease / Q000503:physiopathology*; D051381:Rats; D011954:Receptors, Dopamine / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D011954:Receptors, Dopamine; D007501:Iron; D004298:Dopamine