medigraphic.com

2010, Number 3

<< Back

Rev Educ Bioquimica 2010; 29 (3)

Modelos neurotóxicos de la enfermedad de parkinson y disfunción mitocondrial

Alarcón AA, Santamaría ÁA, Königsberg FM

Language: Spanish
References: 26
Page: 92-100
PDF size: 334.89 Kb.


ABSTRACT

Most neurodegenerative disorders are characterized by the progressive atrophy of specific neuronal populations. These events currently lead to the interruption of specific neuronal pathways as well as the expression of several neurological deficits and disorders. Parkinson’s disease is the second more frequent neurodegenerative disease worldwide affecting mature people. Unfortunately, up to now there are not efficient therapeutic drugs available that can counteract its progression. In order to investigate the causes and origins of this disorder, several neurotoxic models mimicking some characteristics of the disease have been used in rodents and non-human primates. Currently, it is known that the mechanisms of action exerted by most of the employed toxicants for this purpose involve the inhibition of mitochondrial complex I and the generation of reactive oxygen species; hence, the role of mitochondrial dysfunction in the development of Parkinson’s disease is fundamental. In this work we will bring a brief review on these models and their relevance for the study of this disorder, giving special attention to the alterations in mitochondrial function.


REFERENCES

  1. Schapira AH, Olanow AW (2004) Neuroprotection in Parkinson disease: mysteries, myths, and misconceptions. JAMA 291:358-364.

  2. Eriksen JL, Wszolek Z, Petrucelli L (2009) Molecular Pathogenesis of Parkinson Disease. Arch Neurol 62:353-357.

  3. Lim SY, Fox SH, Lang AE (2009) Overview of the extranigral aspects of Parkinson disease. Arch Neurol 66:167-172.

  4. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39: 889-909.

  5. Aron L, Klein P, Pham TT, Kramer ER, Wurst W, Klein R (2010) Pro-survival role for Parkinson’s associated gene DJ-1 revealed in trophically impaired dopaminergic neurons. Plos Biol 8:1000349.

  6. Chio JS, Park C, Jeong JW (2009) AMP-activated protein kinase is activated in Parkinson’s disease models mediated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Biochem Biophys Res Commun 391:147-151.

  7. Przedborski S, Vila M (2003) The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model: a tool to explore the pathogenesis of Parkinson’s disease. Ann N Y Acad Sci 991:189-198.

  8. Blesa J, Juri C, Collantes M, Peñuelas I, Prieto E, Iglesias E, Martí-Climent J, Arbizu J, Zubieta JL, Rodríguez-Oroz MC, García-García D, Richter JA, Cavada C, Obeso JA. (2010) Progression of dopaminergic depletion in a model of MPTP-induced Parkinsonism in non-human primates. An (18)F-DOPA and (11)C-DTBZ PET study. Neurobiol Dis. [Epub ahead of print] doi:10.1016/j.nbd.2010.03.006

  9. Schildknecht S, Pöltl D, Nagel DM, Matt F, Scholz D, Lotharius J, Schmieg N, Salvo-Vargas A, Leist M. (2009) Requirement of a dopaminergic neuronal phenotype for toxicity of low concentrations of 1-methyl-4-phenylpyridinium to human cells. Toxicol Appl Pharmacol 241:23-35.

  10. Pothakos K, Kurz MJ, Lau YS (2009) Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson’s disease with severe neurodegeneration. BMC Neurosci 10:16.

  11. Zhang X, Zhou JY, Chin MH, Schepmoes AA, Petyuk VA, Weitz KK, Petritis BO, Monroe ME, Camp DG, Wood SA, Melega WP, Bigelow DJ, Smith DJ, Qian WJ, Smith RD (2010) Region-specific protein abundance changes in the brain of MPTP-induced Parkinson’s disease mouse model. J Proteome Res 9:1496-1509.

  12. Nicklas WJ, Saporito M, Basma A, Geller HM, Heikkila RE (1992) Mitochondrial mechanisms of neurotoxicity Ann N Y Acad Sci 648:28-36.

  13. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306.

  14. Dukes AA, Korwek KM, Hastings TG (2005) The effect of endogenous dopamine in rotenone-induced toxicity in PC12 cells. Antioxid Redox Signal 7:630-638.

  15. Pan T, Rawal P, Wu Y, Xie W, Jankovic J, Le W (2009) Rapamycin protects against rotenone-induced apoptosis through autophagy induction. Neuroscience 164:541-551.

  16. Monti B, Gatta V, Piretti F, Raffaelli SS, Virgili M, Contestabile A (2010) Valproic acid is neuroprotective in the rotenone rat model of Parkinson’s disease: involvement of alpha-synuclein. Neurotox Res 17:130-141.

  17. Hertzmann C, Wiens M, Bowering D, Snow B, Calne D (1990) Parkinson’s disease: a case control study of occupational and environmental risk factors. Am J Ind Med 17:349–355.

  18. Dhillon AS, Tarbutton GL, Levin JL, Plotkin GM, Lowry LK, Nalbone JT, Shephered S (2008) Pesticide/environmental exposures and Parkinon´s disease in East Texas. J Agromedicine 13:37-48.

  19. Hattori K, Naguro I, Runchel C, Ichijo H (2009) The roles of ASK family proteins in stress responses and diseases. Cell Commun Signaling 7:9.

  20. Niso-Santano M, González-Polo RA, Bravo-San Pedro JM, Gómez-Sánchez R, Lastres-Becker I, Ortiz-Ortiz MA, Soler G, Morán JM, Cuadrado A, Fuentes JM. (2010) Activation of apoptosis signal-regulating kinase 1 is a key factor in paraquat-induced cell death: Modulation by the Nrf2/Trx axis. Free Radic Biol Med 48:1370–1381.

  21. Ungerstedt U. (1968) 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 5:107-110.

  22. Przedborski S, Ischiropoulos H (2005) Reactive oxygen and nitrogen species: weapons of neuronal destruction in models of Parkinson’s disease. Antioxid Redox Signal 7:685–693.

  23. Alvarez-Fischer D, Henze C, Strenzke C, Westrich J, Ferger B, Höglinger GU, Oertel WH, Hartmann A (2008) Characterization of the striatal 6-OHDA model of Parkinson’s disease in wild type and a-synuclein-deleted mice. Exp Neurol 210:182-193.

  24. O´Keeffe G, Barker RA, Caldwell MA (2009) Dopaminergic modulation of neurogenesis in the subventricular zone of the adult brain. Cell Cycle 15:2888-2894.

  25. Abeliovich A (2010) Parkinon´s disease Mitochondrial damage control. Nature 463:744-745.

  26. Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoSBiol.8.e1000298.




2020     |     www.medigraphic.com