Selective Autophagy in the Pathogenesis of Parkinson's Disease

This chapter explores various aspects of selective autophagy in the pathogenesis of Parkinson's disease. Compensatory activation of the autophagosomal system in general has been reported in many protein conformational disorders. Expression of huntingtin, the protein found in protein inclusions associated with Huntington's disease, results in upregulation of macroautophagy along with the general stimulation of endosomal–lysosomal activity. Two groups have independently shown that the selective suppression of basal macroautophagy in mouse brain causes diffuse accumulation of ubiquitinated abnormal proteins and ubiquitin-positive inclusions, thereby leading to neuronal toxicity and neurodegeneration. Macroautophagy is initially induced in most of these diseases to protect neurons against abnormal toxic proteins, stress and damaged organelles that may cause cell toxicity and apoptosis. It is observed that pharmacological blockage of the catalytic activities of the proteasome results in upregulation of macroautophagy. It is suggested that macroautophagy can be tracked in cultured cells using recombinant Atg proteins fused to fluorescent proteins which allows identification of autophagosomes, the intracellular compartments directly linked to macroautophagy.