Experimental Parkinson’s disease models

Abstract

Parkinson's disease (PD) is a neurodegenerative  disease that develops slowly; however, there is no  efficient method of early diagnosis, nor is there a cure.  It is characterized by the relatively selective loss of  dopaminergic neuronal cells in the substantia nigra pars  compacta and the presence of alpha-synuclein  aggregation named as Lewy bodies and Lewy neurites  in surviving affected neurons. Nigrostriatal  dopaminergic neurodegeneration is shared with other  parkinsonian disorders, including some genetic forms of  parkinsonism, but many of these disorders do not have  Lewy bodies. An ideal animal model for PD, therefore,  should exhibit age-dependent and progressive  dopaminergic neurodegeneration, motor and non-motor  dysfunction, and abnormal alpha-synuclein pathology.  A wide range of neurotoxic agents are used to  induce PD, alterations that are similar with dose  observed in human PD. These agents are classified  mainly by administration route and the species involved.  The toxins that are mainly used in present 6-  hydroxydopamine, 1-Methyl-4-phenyl-1,2,3,6- tetrahydropyridine, rotenone, paraquat, reserpine,  methamphetamine, 3-nitrotyrosine and isoquinoline  derivatives (Tieu, 2011; McDowell and Chesselet, 2012;  Bezard et al. 2013). In addition, viral mediated  expression of human α-synuclein, as well as the  inoculation of pathogenic α-synuclein species from  Lewy bodies of PD patients, for accurately modelling  progressive self-propagating neurodegeneration and  genetic LRRK2 models (PARK8 gene mutation) has  been used (Jiang and Dickson, 2018).  In conclusion, these models are only  approximations, each possibly holding a certain degree  of relevance. Thus, researchers should select models  whose characteristics are most suitable for addressing  the experimental question.