Papel da alfa-sinucleína e da disfunção mitocondrial associada à doença de Parkinson
DOI:
https://doi.org/10.34024/rnc.2012.v20.8280Palavras-chave:
Alfa-Sinucleína, Alfa-SinucleínaMitocôndria, Doença de ParkinsonResumo
A doença de Parkinson (DP) é uma doença neurodegenerativa, crônica e progressiva, associada a uma disfunção do movimento. Caracteriza-se por uma perda selectiva de neurónios dopaminérgicos na substantia nigra e pela presença de corpos de Lewy – agregados maioritariamente compostos pelas proteínas alfa-sinucleína e ubiquitina. Várias hipóteses têm sido propostas para explicar a neurodegenerescência nesta patologia, que envolve factores ambientais (formas esporádicas) e/ou genéticos (formas familiares). A alfa-sinucleína apresenta três mutações que causam a DP na forma autossómica dominante. Para além disso, a duplicação e a triplicação do gene desta proteína estão igualmente associadas às formas familiares da doença. A disfunção mitocondrial tem também sido ligada à DP. Pretende-se assim neste trabalho de revisão clarificar o papel da alfa-sinucleína e sua relação com a disfunção mitocondrial e a DP.
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Rijk MC, Tzourio C, Breteler MMB, Dartigues JF, Amaducci L, Lopez Pousa S, et al. Prevalence of parkinsonism and Parkinson’s disease in Europe: the EUROPARKINSON collaborative study. European Community concerted
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Olanow CW, Tatton WG. Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 1999;22:123-44. http://dx.doi.org/10.1146/annurev.neuro.22.1.123
Dawson TM, Dawson VL. Molecular pathways of neurodegeneration in Parkinson’s disease. Science 2003; 302:819-22. http://dx.doi.org/10.1126/science.1087753
Hardy J, Cookson MR, Singleton A. Genes and parkinsonism. Lancet Neurol 2003;2:221-8. http://dx.doi.org/10.1016/S1474-4422(03)00350-8
Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 1997;276:2045-7. http://dx.doi.org/10.1126/science.276.5321.2045
Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, et al. Alpha-synuclein locus triplication causes Parkinson’s disease. Science 2003;302:841. http://dx.doi.org/10.1126/science.1090278
Ibanez P, Bonnet AM, Debarges B, Lohmann E, Tison F, Pollak P, et al. Causal relation between alpha-synuclein gene duplication and familial Parkinson’s disease. Lancet 2004;364:1169-71.1.Goedert M. Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2001;2:492-501. http://dx.doi.org/10.1038/35081564
Rijk MC, Tzourio C, Breteler MMB, Dartigues JF, Amaducci L, Lopez Pousa S, et al. Prevalence of parkinsonism and Parkinson’s disease in Europe: the EUROPARKINSON collaborative study. European Community concerted
action on the epidemiology of Parkinson´s disease. J Neurol Neurosurg Psychiatry 1997;62:10-15.
Verbaan D, Marinus J, Visser M, van Rooden SM, Stiggelbout AM, van Hilten JJ. Patient-reported autonomic symptoms in Parkinson disease. Neurology 2007;69:329-330. http://dx.doi.org/10.1212/01.wnl.0000266593.50534.e8
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997;388:839-840. http://dx.doi.org/10.1038/42166
Abou-Sleiman PM, Mugit MM, Wood, NW. Expanding insights of mitochondrial dysfunction in Parkinson’s disease. Nat Rev Neurosci 2006;7:207-19. http://dx.doi.org/10.1038/nrn1868
Olanow CW, Tatton WG. Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 1999;22:123-44. http://dx.doi.org/10.1146/annurev.neuro.22.1.123
Dawson TM, Dawson VL. Molecular pathways of neurodegeneration in Parkinson’s disease. Science 2003; 302:819-22. http://dx.doi.org/10.1126/science.1087753
Hardy J, Cookson MR, Singleton A. Genes and parkinsonism. Lancet Neurol 2003;2:221-8. http://dx.doi.org/10.1016/S1474-4422(03)00350-8
Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 1997;276:2045-7. http://dx.doi.org/10.1126/science.276.5321.2045
Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, et al. Alpha-synuclein locus triplication causes Parkinson’s disease. Science 2003;302:841. http://dx.doi.org/10.1126/science.1090278
Ibanez P, Bonnet AM, Debarges B, Lohmann E, Tison F, Pollak P, et al. Causal relation between alpha-synuclein gene duplication and familial Parkinson’s disease. Lancet 2004;364:1169-71.
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Publicado: 2012-03-31