Parkinson Hastalığı ve İlişkili Olduğu Genler

Parkinson Hastalığı, Alzheimer hastalığından sonra ikinci en sık görülen nörodejeneratif bir hastalıktır. Parkinson hastalığının temel patolojik bulguları; orta beyindeki substantia nigra pars compacta ve striatumdaki dopaminerjik nöronların ilerleyici kaybı ve Lewy cisimcikleri olarak adlandırılan inklüzyonların nöronlarda birikimidir. Birçok araştırmacı, Parkinson hastalığının nadiren ailesel olduğunu, özellikle sporadik faktörlerin (çevresel ve genetik) bu hastalığın başlamasına ve ilerlemesine neden olduğunu göstermiştir. Bugüne kadar Parkinson hastalığına bağlı 26 gen lokusu tanımlanmıştır. Bu çalışmanın amacı, Parkinson hastalığı ile ilişkili genler üzerine literatüre katkı sağlamaktır.

Anahtar Kelimeler:

SNCA, Parkinson hastalığı, α-Sinüklein, Lewy cisimcikleri

Parkinson Disease and Associated Genes

Parkinson disease is the second most common neurodegenerative disease after Alzheimer's disease. Essential pathological findings of Parkinson's disease; progressive loss of dopaminergic neurons in the substantia nigra pars compacta and striatum in the midbrain and accumulation of inclusions in the neurons called Lewy bodies. Many researchers have shown that Parkinson's disease is rarely caused by familial, especially sporadic factors (environmental and genetics) contribute to the initiation and progression of this disease. 26 gene loci related to Parkinson's disease have been identified until now. Aims of this study, contributing to the literature on genes associated with Parkinson's disease.

Keywords:

Parkinson disease, SNCA, α-Synuclein, Lewy bodies,

PDF

___

[1] J. Lotharius, P. Brundin, “Impaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson's disease,” Human Molecular Genetics, vol. 11, no. 20, pp. 2395-2407, 2002.
[2] S. Özekmekçi, H. Apaydın , Parkinson Hastalığı Hasta ve Yakınları İçin El Kitabı, 5.baskı, İstanbul, Türkiye: Bayçınar Tıbbi Yayıncılık ve Reklam Hiz. Tic. Ltd. Şti, 2013, ss. 1-5.
[3] K.S. McNaught and C.W Olanow,“Proteolytic Stress: A Unifying Concept for the Etiopathogenesis of Parkinson’s Disease,” Annals of Neurology, vol. 53, no. 3, pp. 73-86, 2003.
[4] M.J. Farrer, “Genetics of Parkinson disease: paradigm shifts and future prospects,” Nature Reviews Genetics, vol. 7, no. 4, pp. 306-318, 2006.
[5] J.M. Shulman, P.L. De Jager, M.B. Feany, “Parkinson’s Disease: Genetics and Pathogenesis,” Annual Review of Pathology: Mechanisms of Disease, vol. 6, pp. 193-222, 2011.
[6] L.M. Bekris, I.F. Mata, C.P. Zabetian, “The Genetics of Parkinson Disease,” Journal of Geriatric Psychiatry and Neurology, vol. 23, no. 4, pp. 228–242, 2010.
[7] W. Dauer and S. Przedborski, “Parkinson’s Disease Mechanisms and Models,” Neuron, vol. 39, pp. 889–909, 2003.
[8] O.B. Tysnes, A. Storstein, “Epidemiology of Parkinson’s disease,” Journal of Neural Transmission, vol. 124, no. 8, pp. 901-905, 2017.
[9] A.H. Rajput, S. Birdi, “Epidemiology of Parkinson’s disease,” Parkinsonism & Related Disorders, vol. 3, no. 4, pp.175-186, 1997.
[10] R. Çakmur, “Parkinson Hastalığının Epidemiyoloisi ve Klinik Özellikleri,” Journal of Neurology, vol. 1 pp. 160-163, 2003.
[11] C.M. Lill, “Genetics of Parkinson's disease,” Molecular and Cellular Probes, vol. 30, pp. 386-396, 2016.
[12] S. Lesagea, and A. Brice, “Role of Mendelian genes in “sporadic” Parkinson’s disease,” Parkinsonism Relat Disorders, vol. 18, no. 1, pp. 66-70, 2012.
[13] M. Spatola, C. Wider, “Genetics of Parkinson’s disease: the yield,” Parkinsonism Relat Disorders, vol. 20, no. 1, pp. 35-38, 2014.
[14] K.R. Kumar, A. Djarmati-Westenberger and A. Grünewald, “Genetics of Parkinson’s Disease,” Seminars in Neurology, vol. 31 no. 5, pp. 433-440, 2011.
[15] C. Klein and A. Westenberger, “Genetics of Parkinson’s Disease,” Cold Spring Harbor Perspectives in Medicine, vol. 2, no. 1, pp. 1-16, 2017.
[16] S. Fujioka, K. Ogaki, P.M. Tacik, R.J. Uitti, O.A. Ross, Z.K Wszolek, “Update on novel familial forms of Parkinson’s disease and multiple system atrophy,” Parkinsonism Relat Disorders, vol. 20, no. 1, pp. 29-34, 2014.
[17 ] S. Lesage, M. Anheim, F. Letournel, L. Bousset, A. Honoré, N. Rozas, L. Pieri, K. Madiona, A. Dürr, R. Melki, C.Verny, and A. Brice, “G51D α-Synuclein Mutation Causes a Novel Parkinsonian–Pyramidal Syndrome,” Annual Neurology, vol. 73, no. 4, pp. 459-471, 2013.
[18] S. Appel-Cresswell, C. Vilarino-Guell, M. Encarnacion, H. Sherman, I. Yu, B. Shah, D. Weir, C. Thompson, C. Szu-Tu, J. Trinh, J.O. Aasly, A. Rajput, A.H. Rajput, A.J. Stoessl, M.J. Farrer, “Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease,” Movement Disorders, vol. 28, no. 6, pp. 811-813, 2013.
[19] D. Hoffman-Zacharska, D. Koziorowski, O.A. Ross, M. Milewski, J. Poznański, M. Jurek, Z.K. Wszolek, A. Soto-Ortolaza, J. Sławek, P. Janik, Z. Jamrozik, A. Potulska-Chromik , B. Jasińska-Myga, G. Opala, A. Krygowska-Wajs, K. Czyżewski, D.W. Dickson, J.Bal, A. Friedman, “Novel A18T and pA29S substitutions in α-synuclein may be associated with sporadic Parkinson's disease,” Parkinsonism Relat Disorders, vol. 19, no. 11, pp. 1057-1060, 2013.
[20] S. Saiki, S.Sato, N.Hattori, “Molecular pathogenesis of Parkinson's disease: update,” Journal of Neurology, Neurosurgery, and Psychiatry, vol. 83, no. 4, pp. 430-436, 2012.
[21] J.J. Zarranz, J. Alegre, J.C. Gómez-Esteban, E. Lezcano, R. Ros, I. Ampuero, L. Vidal, J. Hoenicka, O. Rodriguez, B. Atarés, V. Llorens, G.E. Tortosa, T. del Ser, D.G. Muñoz, J.G. de Yebenes, “The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia,” Annul Neurology vol. 55, no. 2, pp. 164-173, 2004.
[22] H. Deng H and L. Yuan, “Genetic variants and animal models in SNCA and Parkinson disease,” Ageing Research Reviews, vol. 15, pp. 161-176, 2014.
[23] A.B. Singleton, M. J. Farrer, V. Bonifati, “The genetics of Parkinson's disease: progress and therapeutic implications,” Movement Disorders, vol. 28, no. 1, pp. 14-23, 2013.
[24] C. Schulte and T. Gasser, “Genetic basis of Parkinson’s disease: inheritance, penetrance, and expression,” The Application of Clinical Genetics, vol. 4, pp. 67-80, 2011.
[25] C. Vilarino-Guell, C. Wider, O.A. Ross, J.C. Dachsel, J.M. Kachergus, S.J. Lincoln, I. A. Soto-Ortolaza, A. S. Cobb, G.J. Wilhoite, J. A. Bacon, B. Beharouz, H.L. Melrose, E. Hentati, A. Puschmann, D.M. Evans, E. Conibear, W.W. Wasserman, J.O. Asly and M. J. Farrer, “VPS35 mutations in Parkinson disease,” The American Journal of Human Genetics, vol. 89, pp. 162-167, 2011.
[26] C. Popescu, “Mechanisms Implicated in Parkinson Disease from Genetic Perspective,” Medical & Clinical Reviews. vol. 2, no. 3, pp. 1-17, 2016.
[27] A. Samii, J.G. Nutt, B.R. Ransom, “Parkinson's disease,” Lancet, vol. 363, no. 9423, pp. 1783-1793, 2004.
[28] S. Lubbe, H.R. Morris, “Recent advances in Parkinson’s disease genetics,” Journal of Neurology, vol. 261, no. 2, pp. 259-266, 2014.
[29] D.G. Hernandez, X. Reed and A.B. Singleton AB, “Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance,” Journal of Neurochemistry, vol. 139, no. 1, pp. 59-74, 2016.
[30] S. Shojaee, F. Sina, S.S. Banihosseini, M.H. Kazemi, R. Kalhor, G. A. Shahidi, H. Fakhrai-Rad, M. Ronaghi and E. Elahi, “Genome-wide linkage analysis of a Parkinsonian-pyramidalsyndrome pedigree by 500 K SNP arrays,” American Journal of Human Genetics, vol. 82, no. 6, pp. 1375–1384, 2008.
[31] V.S. Burchell, D.E. Nelson, A. Sanchez-Martinez, M.D. Camprubi, R. M. Iwatt, J.H. Pogson, S. J. Randle, S. Wray, P.A. Lewis, H. Houlden, A.Y. Abramov, J. Hardy, N.W. Wood, A.J. Whitworth, H. Leman and H P. Favreau, “The Parkinson’s disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy,” Nature Neuroscience, vol. 16, pp. 1257–1265, 2013.
[32] Z.D. Zhou, S.P. Xie, S. Sathiyamoorthy, W.T. Saw, T.Y. Sing, S.H.Ng, H.P. Chua, A.M. Tang, F. Shaffra, Z. Li, H. Wang, P.G. Ho, M.K. Lai, D.C. Angeles, T.M. Lim, E.K. Tan, “F-box protein 7 mutations promote protein aggregation in mitochondria and inhibit mitophagy,” Human Molecular Genetics, vol. 24, pp. 6314–6330, 2015.
[33] A. Goris, C.H. Williams-Gray, G.R. Clark, T. Foltynie, S.J. Lewis, J. Brown, M. Ban, M.G. Spillantini, A. Compston, D.J. Burn, P.F. Chinnery, R.A. Barker, S.J. Sawcer, “Tau and alpha-synuclein in susceptibility to, and dementia in, Parkinson's disease,” Annals Neurology, vol. 62, no. 2, pp. 145-153, 2007.