Animal Models for Parkinson's Disease

Parkinson's disease (PD) is a chronic neurodegenerative disease with major impacts on patients' lives and on society as a whole. It is one of the most common neurodegenerative diseases in the world, second only to Alzheimer's disease. Low levels of production of dopamine (DA) are associated with PD. This is caused by a progressive loss of neurons in the midbrain's substantia nigra, resulting in changes in neural conduction within the nigrostriatum. Research into PD has been going on since 1960, still there is no cure although the symptoms can be effectively controlled and the severity of the affliction can be reduced. The main obstacle in the development of neuroprotective therapy is a limited understanding of the key molecular events that provoke neurodegeneration. A misfolding of proteins and dysfunction of the ubiquitin-proteasome pathway are the critical factors in the pathogenesis of PD. Neurotoxic models (particularly 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) have been very useful in elucidating the molecular cascade of cell death in dopaminergic neurons. They are also of use in efforts to limit the progression of the disease and to prevent the long-term functional and pathological outcome in PD. The establishment of animal and cellular models of mutations in LRRK2 and alpha-synuclein, and mutations in parkin, DJ-1 and PINK1, has been of use in elucidating the molecular mechanisms of this disorder, and research using these models is providing new ideas about the pathogenesis of PD. Several researchers are synthesizing and screening novel derivatives for their antiparkinsonian potential using different animal models. In this work we describe different animal models used in assessing the antiparkinson activity of novel therapeutic treatments.