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Neuroscience Laboratory Services

Parkinson's Disease

Preclinical Models of PD

Unique Approaches To Modeling Parkinson's Disease

Parkinson’s Disease (PD) is typically an adult-onset progressive neurodegenerative movement disorder that affects millions of people worldwide. Pathologically, PD is characterized by the profound and specific loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain. The cardinal symptoms of PD include bradykinesia, resting tremor, rigidity, and postural instability. To date, research into the etiology of PD has revealed that most cases are sporadic, though some thirteen genetic loci have been identified to be disease-related. Examination of the biochemical properties of these mutant proteins and the pathways in which they are involved has led to the uncovering of three basic pathogenetic pathways common to both heritable and idiopathic forms of PD: abnormal protein control, mitochondrial dysfunction, and altered kinase activity. 

Progress towards the identification of disease-related genes has thus led to the expansion of animal models of PD from the classic 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA)-induced neurotoxin models to genetic models of the disease. Due to its complex pathology, however, there is no animal disease model that replicates all aspects of human PD. With the evolution of such models, converging lines of evidence from toxin-induced and genetic models have continued to further our understanding of the pathological processes underlying PD and lend themselves as useful systems for the examination of therapeutic interventions. 
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