%0 Journal Article
%T Toxin-Induced and Genetic Animal Models of Parkinson's Disease
%A Shin Hisahara
%A Shun Shimohama
%J Parkinson's Disease
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/951709
%X Parkinson's disease (PD) is a common progressive neurodegenerative disorder. The major pathological hallmarks of PD are the selective loss of nigrostriatal dopaminergic neurons and the presence of intraneuronal aggregates termed Lewy bodies (LBs), but the pathophysiological mechanisms are not fully understood. Epidemiologically, environmental neurotoxins such as pesticides are promising candidates for causative factors of PD. Oxidative stress and mitochondrial dysfunction induced by these toxins could contribute to the progression of PD. While most cases of PD are sporadic, specific mutations in genes that cause familial forms of PD have led to provide new insights into its pathogenesis. This paper focuses on animal models of both toxin-induced and genetically determined PD that have provided significant insight for understanding this disease. We also discuss the validity, benefits, and limitations of representative models. 1. Introduction Parkinson¡¯s disease (PD) is one of the most common chronic neurodegenerative disorders. It is characterized by a variety of motor (bradykinesia, rigidity, tremor, and postural instability) and nonmotor (autonomic disturbances and psychosis) symptoms. Although it can be diagnosed accurately, no therapeutic strategies can cure or completely block the progression of PD. Pathologically, PD is characterized by the severe loss of dopaminergic (DAergic) neurons in the pars-compacta nigra and the presence of proteinaceous ¦Á-synuclein inclusions, called Lewy bodies (LBs), which are present in neurons of the central nervous system (specific cortical regions, brain stem, and spinal cord), peripheral autonomic nervous system, enteric nervous system (ENS), and cutaneous nerves [1¨C3]. Similar to other neurodegenerative diseases, such as Alzheimer¡¯s disease, age is the major risk factor for PD although 10% of the people with the disease are younger than 45. Although PD is regarded as a sporadic disorder, remarkably few environmental causes or triggers have been identified [4¨C6]. Pesticides and herbicides are the most likely candidates for environmental agents associated with the pathogenesis of PD. On the other hand, PD characteristics are seen in a number of familial motor disorders caused by different genetic factors. Animal models of neurodegenerative diseases, including PD, have in general been quite instructive in understanding their pathogenesis. Ideally, animal models of PD, whether induced by environmental risk factors (neurotoxins) or genetic manipulations, should faithfully reproduce the clinical manifestations (behavioral
%U http://www.hindawi.com/journals/pd/2011/951709/