Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2006, vol. 15, nr 4, July-August, p. 705–709

Publication type: review article

Language: English

Parkinson’s Disease as a Consequence of Impaired Redox Homeostasis in the Brain

Choroba Parkinsona jako rezultat zaburzenia homeostazy red−ox mózgu

Agata Kochman1,, Monika Wilczyńska1,, Joanna Syrycka1,, Anil Kumar Agrawal2,3,

1 Department of Pathological Anatomy, Silesian Piasts University of Medicine in Wrocław, Poland

2 Second Department of General and Oncological Surgery, Silesian Piasts University of Medicine in Wrocław, Poland

3 Department of Medical Emergency, Faculty of Public Health, Silesian Piasts University of Medicine in Wrocław, Poland

Abstract

Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders of advanced age. Clinically, PD is characterized by akinesia, resting tremor, and rigidity. A characteristic feature of PD is loss of pigmented neurons in the substantia nigra. A review of available data on PD shows that multiple factors are involved in maintaining the redox state of the brain, and impairment of any of these components may result in PD. This includes changes in the neuromelanin level, iron level, mitochondrial function, dopamine and tyrosine metabolism, and inflammation. This mini−review presents some new aspects of the relationship between impairment of brain redox homeostasis and PD.

Streszczenie

Choroba Parkinsona (PD) jest jedną z najczęstszych chorób degeneracyjnych mózgu zaawansowanego wieku. Klinicznie PD charakteryzuje się akinezją, drżeniem spoczynkowym i sztywnością. Charakterystyczną cechą PD jest utrata barwnika neuronów w obrębie substantia nigra. Z dostępnych danych na temat PD wynika, że za utrzymanie równowagi red−ox w mózgu odpowiedzialnych jest wiele czynników, a zaburzenie któregokolwiek z nich może spowodować rozwój PD. Zalicza się do nich: neuromelaninę, stężenie żelaza, funkcję mitochondriów, metabolizm dopaminy i tyrozyny oraz procesy zapalne. Ta praca poglądowa ukazuje niektóre nowe aspekty związku między zaburzeniem homeostazy red−ox a PD.

Key words

Parkinson’s disease, free radicals, neuromelanin, mitochondria, iron

Słowa kluczowe

choroba Parkinsona, wolne rodniki, neuromelanina, mitochondria, żelazo

References (33)

  1. Hughes AJ, Daniel SE, Blankson S, Lees AJ: A clinicopathologic study of 100 cases of Parkinson’s disease. Arch Neurol 1993, 50, 140–148.
  2. Blum D, Torch S, Lamberg N, Nisson MF, Benabid AL, Sadoul R, Verna JM: Molecular pathways involved in the neurotoxicity of 6−OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Neurobiology 2001, 65, 135–172.
  3. Agid Y: Aging, disease and nerve death. Bull Acad Natl Med 1995, 179, 1193–1203.
  4. Ilic TV, Jovanovic M, Jovicic A, Tomovic M: Oxidative stress indicators are elevated in de novo Parkinson’s disease patients. Funct Neurol 1999, 14, 141–147.
  5. Enochs WS, Sarna T, Zecca L, Riley PA, Swartz HM: The roles of neuromelanin, binding of metal ions, and oxidative cytotoxicity in the pathogenesis of Parkinson’s disease: a hypothesis. J Neural Transm Park Dis Dement Sect 1994, 7, 83–100.
  6. Fornstedt B, Brun A, Rosengren E, Carlsson A: The apparent autoxidation rate of catechols in dopamine−rich regions of human brains increases with the degree of depigmentation of substantia nigra. J Neural Transm Park Dis Dement Sect 1989, 1, 279–295.
  7. Fahn S, Cohen G: The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 1992, 32, 804–812.
  8. Korytkowski W, Sama T, Zaremba M: Antioxidant action of neuromelanin: the mechanism of inhibitory effect on lipid peroxidation. Arch Biochem Biophys 1995, 319, 142–148.
  9. Nguyen A, Gille G, Moldzio R, Hunh S−T, Rausch W−D: Synthetic neuromelanin is toxic to dopaminergic cell cultures. J Neural Transm 2002, 109, 651–661.
  10. Cheng N, Maeda T, Kume T, Kaneko S, Kochiyama H, Akaike A, Goshima Y, Misu Y: Differential neurotoxicity induced by L−dopa and dopamine in cultured striatal neurons. Brain Res 1996, 743, 278–283.
  11. Kochman A, Segura−Aguillar H, Metodiewa D: Metabolism of dopamine and its derivative in model systems: involvement of superoxide and reduced glutathione. Zjazd Streszczenia (XXXVII Zjazd PTBioch Toruń 10–14 IX 2001) 2001, No: P−14B−49.
  12. Jones DC, Gunasekar PG, Borowitz JL, Isom GE: Dopamine−induced apoptosis is mediated by oxidative stress and is enhanced by cyanide in differentiated PC12 cells. J Neurochem 2000, 76, 2296–2304.
  13. Kostrzewa RM, Brus R, Kostrzewa JP: Insidious dopamine: provocateur or protective agent in Parkinson’s disease? Pol J Pharmacol 2001, 53, 165–166.
  14. Lenaz G: The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. JUBMB Life 2001, 52, 159–164.
  15. Hattori N, Tanaka M, Ozawa T, Mizuno Y: Immunohistochemical studies on complexes I, II, III and IV of mitochondria in Parkinson’s disease. Ann Neurol 1991, 30, 563–571.
  16. Beal MF: Aging, energy, and oxidative stress in neurodegenerative diseases. Ann Neurol 1995, 38, 357–366.
  17. Beal MF, HymanBT, Koroshetz W: Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? Trends Neurosci 1993, 16, 125–131.
  18. Davis W Jr, Ronai Z, Tew KD: Cellular thiols and reactive oxygen species in drug−induced apoptosis. J Pharmacol Exp Ther 2001, 296, 1–6.
  19. Mytilineou C, Kramer B, Yabut J: Glutathione depletion and oxidative stress. Parkinsonism Relat Disord 2002, 8, 385.
  20. Segura−Aguilar J, Metodiewa D, Baez S: The possible role of one−electron reduction of aminochrome in the neurodegenerative process of dopaminergic system. Neurotoxicity Res 2001, 3, 157–166.
  21. Winterbourn CC, Metodiewa D: Reactivity of biologically important thiol compounds with superoxide and hydrogen peroxide. Free Rad Biol Med 1997, 27, 322–328.
  22. Hayes JD, McLellan LI: Glutathione and glutathione−dependent enzymes represent a co−ordinately regulated defense against oxidative stress. Free Rad Biol Med 1999, 31, 273–300.
  23. Hochman A, Sternin H, Gorodin S, Korsmeyer S, Ziv I, Melamed E, Offen D: Enhanced oxidative stress and altered antioxidants in brains of Bcl−2−deficient mice. J Neurochem 1998, 71, 741–748.
  24. Aime S, Bergamasco B, Bigliano D: EPR investigations of the iron domain in neuromelanin. Biochim Biophys Acta Mol Basis Dis 1997,1361, 49–58.
  25. Jellinger KA, Stadelmann CH: Mechanisms of cell death in neurodegenerative disorders. J Neural Transm 2000, 59, 95–114.
  26. Njus D, Kelley PM, Harnadek GJ, Pacquing YV: Mechanism of ascorbic acid regeneration mediated by cytochrome b561. Ann N Y Acad Sci 1987,493, 108–119.
  27. Ponting CP: Domain homologues of dopamine beta−hydroxylase and ferric reductase: roles for iron metabolism in neurodegenerative disorders? Hum Mol Genet 2001, 10, 1853–1858.
  28. Goldstein S, Czapski G, Lind J, Merényi G: Tyrosine nitration by simultaneous generation of NO
  29. Krainev AG, Williams TD, Bigelow DJ: Enzymatic reduction of 3−nitrotyrosine generates superoxide. Chem Res Toxicol 1998, 11, 495–502.
  30. Santos CXC, Bonini MG, Augusto O: Role of the carbon radical anion in tyrosine nitration and hydroxylation by peroxynitrite. Arch Biochem Biophys 2000, 377, 146–152.
  31. Kurkowska−Jastrzebska I, Wronska A, Kohutnicka M, Czlonkowski A, Czlonkowska A: MHC class II positive microglia and lymphocytic infiltration are present in the substantia nigra and striatum in mouse model of Parkinson’s disease. Acta Neurobiol Exp 1999, 59, 1–8.
  32. Le W, Rowe D, Xie W, Ortiz I, He Y, Appel SH: Microglial activation and dopaminergic cell injury: an in vitro model relevant to Parkinson’s disease. J Neurosci 2001, 21, 8447–8455.
  33. Hartmann A, Troadec JD, Hunot S, Kikly K, Faucheux BA, Mouatt−Prigent A, Ruberg M, Agid Y, Hirsch EC: Caspase−8 is an effector in apoptotic death of dopaminergic neurons in Parkinson’s disease, but pathway inhibition results in neuronal necrosis. J Neurosci 2001, 21, 2247–2255.
© Wroclaw Medical University