Overview: cell-based models of parkinson's disease

This chapter presents an overview of cell-based models and pathogenic mechanisms in Parkinson's disease (PD). The cell-based models are particularly valuable in tracking the consequences of toxin exposure and genetic mutations in a cellular environment. The advantage of cell lines is ease of generation, phenotypic homogeneity transfectability, and accessibility to pharmacological manipulation as well as physiological and anatomical analysis. The utility of cell-based models in the pursuit of genetic mechanisms in PD is perhaps stronger, as the basic function of most of the proteins encoded by these genes is being explored. The role of interacting proteins and aging in determining the functional consequences of mutations linked to PD is analyzed. A summary of work with primary cultures of mesencephalic dopaminergic neurons examining the cascade of events triggered by mitochondrial toxins is presented. It is found that fox2a haploinsufficiency leads to a late onset degeneration of mesencephalic dopaminergic neurons and a Parkinsonian phenotype.