Title: Impaired Systemic Iron Homeostasis and Parkinson's Disease
Authors: Mohit Kumar Gangania, Jyoti Batra, Suman Kushwaha, Rachna Aggarwal
DOI: https://dx.doi.org/10.18535/jmscr/v5i4.180
Abstract
Introduction: Parkinson's disease is second most prevalent neurodegenerative old age disorder of basal ganglia characterized by tremor at rest, muscle rigidity, slowness of movement (bradykinesia, akinesia), and changes in posture (instability) which involves α-synuclein protein oligomers and intercellular inclusions known as "Lewy bodies" in substantia nigra and caudate nuclei that is progressive in nature. Both excess and deficiency in levels of transition metals (especially iron) can be detrimental to the central nervous system (CNS). Abnormalities in iron metabolism have been reported to produce oxidative stress which is one of the major cause in pathogenesis of Parkinson's disease.
Material & Method: In the present study 79 PD patients and 80 controls of Northern Indian population were included and serum levels of Transferrin, TIBC, iron, Transferrin saturation, Ferritin were measured.
Results: In this study, we observed elevated levels of Transferrin (p< 0.001), TIBC (p< 0.001) while reduction in iron (p< 0.001), Transferrin saturation (p< 0.001), Ferritin (p< 0.023) levels in serum of PD patients compared to the controls.
Conclusion: These results suggest the decreased iron concentrations in the peripheral blood, indicating that the iron accumulation in the brain is not dependent of an iron overload, but probably due to impaired iron homeostasis.
Keywords: Parkinson’s Disease, Transferrin, TIBC, iron, Transferrin saturation, Ferritin, Oxidative Stress .
References
1. Kehrer JP. The Haber–Weiss reaction and mechanisms of toxicity. Toxicology. 2000; 149(1) :43–50.
2. Halliwell B. Free radicals and antioxidants: a personal view. Nutr Rev. 1994;52(8):253–65.
3. Oakley AE, Collingwood JF, Dobson J, Love G, Perrott HR, Edwardson JA, et al. Individual dopaminergic neurons show raised iron levels in Parkinson disease. Neurology. 2007;68(21):1820–5.
4. Pichler I, Fabiola Del Greco M, Gögele M, Lill CM, Bertram L, Do CB, Eriksson N, Foroud T, Myers RH, Nalls M, Keller MF. Serum iron levels and the risk of Parkinson disease: a mendelian randomization study. PLoS Med. 2013 Jun 4;10(6):e1001462.
5. Koziorowski D, Friedman A, Arosio P, Santambrogio P, Dziewulska D. ELISA reveals a difference in the structure of substantia nigra ferritin in Parkinson's disease and incidental Lewy body compared to control. Parkinsonism & related disorders. 2007 May 31;13(4):214-8.
6. Uversky VN, Li J, Fink AL. Metal-triggered structural transfor- mations, aggregation, and fibrillation of human a-synuclein a possible molecular link between Parkinson’s disease and heavy metal exposure. J Biol Chem. 2001;276(47):44284–96.
7. Richardson DR. Novel chelators for central nervous system dis- orders that involve alterations in the metabolism of iron and other metal ions. Ann N Y Acad Sci. 2004;1012(1):326–41.
8. Jimenez-Jimenez FJ, Molina JA, Aguilar MV, Meseguer I, Mateos-Vega CJ, Gonzalez-Munoz MJ, et al. Cerebrospinal fluid levels of transition metals in patients with Parkinson’s disease. J Neural Transm. 1998;105(4–5):497–505.
9. Logroscino G, Marder K, Graziano J, Freyer G, Slavkovich V, Lolacono N, et al. Altered systemic iron metabolism in Parkinson’s disease. Neurology. 1997;49(3):714–7.
10. Hegde ML, Shanmugavelu P, Vengamma B, Rao TS, Menon RB, Rao RV, et al. Serum trace element levels and the complexity of inter-element relations in patients with Parkinson’s disease. J Trace Elem Med Biol. 2004;18(2):163–71.
11. Logroscino G, Marder K, Graziano J, Freyer G, Slavkovich V, LoIacono N, Cote L, Mayeux R. Altered systemic iron metabolism in Parkinson's disease. Neurology. 1997 Sep 1;49(3):714-7.
12. Tórsdóttir G, Kristinsson J, Sveinbjörnsdóttir S, Snaedal J, Jóhannesson T. Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. Basic & Clinical Pharmacology & Toxicology. 1999 Sep 1;85(s1):239-43.
13. Weinreb O, Mandel S, Youdim MB, Amit T. Targeting dysregulation of brain iron homeostasis in Parkinson's disease by iron chelators. Free Radical Biology and Medicine. 2013 Sep 30;62:52-64.
14. Savica R, Grossardt BR, Carlin JM, Icen M, Bower JH, Ahlskog JE, Maraganore DM, Steensma DP, Rocca WA. Anemia or low hemoglobin levels preceding Parkinson disease A case-control study. Neurology. 2009 Oct 27;73(17):1381-7.