Excitotoxicity

Parkinson’s disease (PD) is a multisystem, complex disorder with an uncertain etiology characterized by the involvement of selected neuronal populations throughout the central and peripheral nervous systems. The main pathological feature of the disease is degeneration of dopaminergic, melanized neurons of the substantia nigra pars compacta (SNc) projecting to the corpus striatum; this is associated with the presence of intracytoplasmic, proteinaceous inclusions termed Lewy bodies (LBs), presenting as spherical, eosinophilic structures with a central, granular core surrounded by a fibrillary halo (Betarbet et al., 2002; Hirsch, 1999; Jellinger, 1998; Riederer and Lange, 1992). The striatal dopaminergic denervation resulting from the SNc cell loss triggers complex functional modifications within the basal ganglia circuitry that cause the typical motor symptoms of the disease (tremor, rigidity, and bradykinesia) (Blandini et al., 2000). Although PD is the prototypical movement disorder, the disease is also characterized by numerous nonmotor symptoms, which include autonomic dysfunction, sleep disorders, psychiatric symptoms, gastrointestinal dysfunction, and cognitive dysfunction (Poewe, 2008).