Abstract
It has become increasingly evident that proteolytic events are primary mechanisms in the development of major neurodegenerative diseases that include Alzheimer’s disease (AD), Huntington’s disease (HD), and Parkinson’s disease (PD). This chapter will illustrate the theme that proteolytic mechanisms are primary contributors to the pathogenesis of AD, HD, and PD (Fig. 1). In each of these diseases, genetic mutations result in expression of protein precursors that undergo limited proteolysis to result in the formation of neurotoxic peptides. Of paramount importance is the deposition of each of these toxic peptide fragments as protein aggregates in the brain, which are manifested as specific neuropathologies. These gene mutations and resultant peptide fragments eventually contribute to the behavioral abnormalities that are characteristic of each of these neurodegenerative diseases — AD, HD, and PD (Table 1).
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