The four horsemen of neurodegenerative diseases Alzheimer, Parkinson, Huntington and amyotrophic lateral skleroz; clinical definition and experimental models

Öz

Along with the increase in the life span in the world and our country, the elderly population brings with different problems. During this life span destruction of nerve cells and clinical manifestations revealing after that constitute the group of diseases called "neurodegenerative diseases". Some neurodegenerative diseases are related to genetic factors rather than age. The emergence mechanisms of these diseases and development of new therapies are only possible by establishing experimental models capable of work in experimental animals. In this review, clinical features of neurogenerative diseases and pharmalogical/transgenic methods used in experimental model of neurodegenerative diseases will be mentioned.

Anahtar Kelimeler

• Experimental models
• neurodegeneration
• neurodegenerative diseases

Nörodejeneratif hastalıklarda mahşerin 4 atlısı Alzheimer, Parkinson, Huntington ve amiyotrofik lateral skleroz: Klinik tanımlama ve deneysel modeller

Öz

Dünyada ve ülkemizde yaşam süresinin artışı ile birlikte yaşlı nüfus beraberinde farklı sorunlar da getirmektedir. Bu uzun yaşam süresi boyunca oluşan sinir hücrelerinin harabiyeti ve sonucunda ortaya çıkan klinik tablolar “nörodejeneratif hastalıklar” denilen hastalık grubunu oluşturmaktadır. Bazı nörodejeneratif hastalıklar ise yaşlanmadan çok genetik faktörlerle ilişkilidir. Bu hastalıkların oluşum mekanizmalarının ortaya konması ve yeni tedavilerin geliştirilmesi ancak bu hastalıkları deney hayvanlarında çalışmayı mümkün kılacak deneysel modellerin oluşturulmasıyla mümkündür. Bu derlemede, nörodejeneratif hastalıkların kliniği ve deneysel modellemesinde kullanılan farmakolojik/transgenik yöntemlere değinilecektir.

Anahtar Kelimeler

• Deneysel modeller
• nörodejenerasyon
• nörodejeneratif hastalıklar

Kaynakça

1. 1. Shamim IA. Neurodegenerative Diseases. New York: Springer; 2012.
2. 2. Avila J, Lucas J, Hernandes F. Animal Models for Neurodegenerative Disease. Cambridge: The Royal Society of Chemistry; 2011.
3. 3. Hardiman O, Doherty CP, Elamin M, Bede P. Neurodegenerative Disorders. Switzerland: Springer International Publishing; 2016.
4. 4. Cankurtaran M, Arıo¤ul S. Alzheimer hastalı¤ı ve demans tedavisinde yenilikler. Türkiye Tıp Dergisi 2002;9:128-36.
5. 5. Perl DP. Neuropathology of Alzheimer's Disease. Mt Sinai J Med 2010;77:32-42.
6. 6. ahin . Deneysel Alzheimer Hastalı¤ı Modelleri. Turkiye Klinikleri Journal of Neurology Special Topics 2012;5:102-6.
7. 7. Puzzo D, Gulisano W, Palmeri A, Arancio O. Rodent models for Alzheimer's disease drug discovery. Expert Opin Drug Discov 2015;10:703-11.
8. 8. Chesselet MF, Carmichael ST. Animal models of neurological disorders. Neurotherapeutics 2012;9:241-4.

9. 9. Bajo R, Pusil S, López ME, Canuet L, Pereda E, Osipova D, et al. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer's disease. Sci Rep 2015;5:9748.
10. 10. McGowan E, Eriksen J, Hutton M. A decade of modeling Alzheimer's disease in transgenic mice. Trends Genet 2006;22:281-9.
11. 11. Victor S. Van Laar, Sarah B. Berman. Mitochondrial dynamics in Parkinson's disease. Exp Neurol 2009;218:247–56.
12. 12. Wakabayashi K, Tanji K, Odagiri S, Miki Y, Mori F, Takahashi H. The Lewy body in Parkinson's disease and related neurodegenerative disorders. Mol Neurobiol 2013;47:495-508.
13. 13. Gubellini P, Kachidian P. Animal models of Parkinson's disease: An updated overview. Revue Neurologique 2015;171:750-61.
14. 14. Jackson-Lewis V, Blesa J, Przedborski S. Animal models of Parkinson's disease. Parkinsonism Relat Disord 2012;18:183-5.
15. 15. Blandini F, Armentero MT. Animal models of Parkinson's disease. FEBS J 2012;279:1156-66.
16. 16. Lindgren HS, Lelos MJ, Dunnett SB. Do a-synuclein vector injections provide a better model of Parkinson's disease than the classic 6-hydroxydopamine model? Exp Neurol. 2012;237:36-42.
17. 17. Sanchez-Betancourt J, Anaya-Martínez V, Gutierrez-Valdez AL, Ordoñez-Librado JL, Montiel-Flores E, Espinosa-Villanueva J, et al. Manganese mixture inhalation is a reliable Parkinson disease model in rats. Neurotoxicology 2012;33:1346-55.
18. 18. Pickrell AM, Pinto M, Moraes CT. Mouse models of Parkinson's disease associated with mitochondrial dysfunction.Mol Cell Neurosci 2013;55:87-94.
19. 19. Ersoy N, Baak AN. Molecular Biology of Huntington's Disease. Turk J Neurol 2005;11:27-44.
20. 20. Pouladi MA, Morton AJ, Hayden MR. Choosing an animal model for the study of Huntington's disease. Nature Reviews. Neuroscience 2013;14:708–21.
21. 21. Mehrotra A, Sood A, Sandhir R. Mitochondrial modulators improve lipid composition and attenuate memory deficits in experimental model of Huntington’s disease. Molecular and Cellular Biochemistry 2015;410:281-92.
22. 22. Li JY, Popovic N, Brundin P. The use of the R6 transgenic mouse models of Huntington's disease in attempts to develop novel therapeutic strategies. NeuroRx 2005;2:447–64.
23. 23. Tiryaki E, Horak HA. ALS and other motor neuron diseases. CONTINUUM: Lifelong Learning in Neurology 2014;20:1185-207.
24. 24. Karlıkaya G, Hays AP. Amiyotrofik lateral skleroz nöropatolojik bir çalıma. Türk Nöroloji Dergisi 2005;11:54-62.
25. 25. Okamoto K, Mizuno Y, Fujita Y. Bunina bodies in amyotrophic lateral sclerosis. Neuropathology 2008;28:109–15.
26. 26. Saberi S, Stauffer JE, Schulte DJ, Ravits J. Neuropathology of amyotrophic lateral sclerosis and its variants. Neurol Clin 2015;33:855-76.
27. 27. Moser JM, Bigini P, Schmitt-John T. The wobbler mouse, an ALS animal model. Molecular Genetics and Genomics 2013;288:207-29.
28. 28. Yang EJ, Choi SM. Synuclein modification in an ALS animal model. Evid Based Complement Altern 2013;2013:1-7.
29. 29. Turner MR, Bowser R, Bruijn L, Dupuis L, Ludolph A, McGrath M, et al. Mechanisms, models and biomarkers in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 2013;14:19-32.
30. 30. Schmitt-John T. VPS54 and the wobbler mouse. Front Neurosci 2015;9:381.
31. 31. Joyce PI, Fratta P, Fisher EM, Acevedo-Arozena A. SOD1 and TDP-43 animal models of amyotrophic lateral sclerosis: recent advances in understanding disease toward the development of clinical treatments. Mamm Genome 2011;22:420-48.
32. 32. Mackenzie IR, Rademakers R. The role of transactive response DNA-binding protein-43 in amyotrophic lateral sclerosis and frontotemporal dementia.Curr Opin Neurol 2008;21:693-700.
33. 33. Liu Y, Pattamatta A, Zu T, Reid T, Bardhi O, Borchelt DR, et al. C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD. Neuron 2016;90:521-34.