ABSTRACT

Identification of genes that cause familial parkinsonism may allow us to identify some of the pathways that lead to nigral degeneration in Parkinson’s disease (PD) and related disorders. One gene in particular, parkin, implicates dysfunction in the ubiquitin-roteasome pathway as a causal route to nigral cell loss as the gene encodes a critical enzyme in this system. Recessive mutations in parkin sensitize cells to proteasome dysfunction and dominant mutations in α-synuclein have similar effects. How we might begin to address some of these questions will be discussed in this chapter.