ReviewFerritin as an important player in neurodegeneration☆
Section snippets
Oxidative stress and the role of iron in neurodegeneration
For decades, oxidative stress has been considered an important factor in the process of neurodegeneration. This theory proposes that an excess of free radicals leads to the death of nerve cells. The imbalance may be caused either by an increased production of free radicals or by insufficient neutralization by scavengers [1]. The human brain seems to be particularly vulnerable to oxidative stress injury because of its high concentrations of lipids and unsaturated fatty acids, of the relatively
Structure and function of ferritin
Ferritins were first identified some 70 years ago, and since then have been well characterized. They are found in almost every living system, with a remarkable conservation of the structure and the capacity to oxidize and incorporate iron. The properties of ferritins in animals, plants and bacteria have been the subject of many reviews and of a recent full issue of Biochimica Biophysica Acta (1800, 8, 2010).
Ferritins are composed of 24 subunits, and form an almost spherical shell delimiting a
Iron and ferritin in normal human brain tissue
Pathologically neurodegenerative diseases, that may be caused by oxidative stress, (Alzheimer’s (AD), PD and atypical parkinsonisms), take place in defined areas of human brain. The hippocampal cortex (Hip) is the most affected brain region in the early phases of AD; PD involves the substantia nigra (SN) and in atypical parkinsonisms other basal ganglia (e.g. globus pallidus GP) are affected as well. Therefore most studies investigating the etiology of neurodegeneration have analyzed these
Neurodegeneration with brain iron accumulation
Neurodegeneration with brain iron accumulation (NBIA) is a group of progressive extrapyramidal and cognitive disorders, which include the previously named Hallervorden–Spatz syndrome, neuroferritinopathy and aceruloplasminemia. The original eponym for the disease acknowledged the work of German neuropathologists Julius Hallervorden and Hugo Spatz. The new term NBIA is now favored in light of the unethical activities of Hallervorden and Spatz before and during World War II.
NBIA are characterized
Conclusions
The possible role of ferritin in neurodegeneration is shown schematically in Fig. 1, and the results of our experimental studies are summarized in Table 4.
There are several pathways leading to neurodegeneration. One of these is oxidative stress injury mediated by Fenton chemistry. Ferritin may play an important role in this process, particularly when mutations or its deregulation lead to inability to maintain iron within ferritin shell. The iron that is not retained may start production of free
Acknowledgments
Andrzej Friedman, Dariusz Koziorowski and Jolanta Galazka-Friedman were partially supported by a grant from Polish Ministry of Science, grant # 2 R. 07. P.W
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The review of this paper was entirely handled by the Co-Editor-in-Chief, Z.K. Wszolek.