M. ANGELA CENCI and MARTIN LUNDBLAD
Parkinson disease (PD) is one of the most common neurodegenerative disorders, affecting about 1% of people over sixty years of age (for review see Bezard et al. 2001; Dauer and Przedborski 2003; Fahn 2003). The disease got its name from the English neurologist James Parkinson, who first described it in 1817 as a "shaking palsy." The characteristic motor symptoms of PD consist of resting tremor, rigidity, hypo- and bradykinesia, and postural abnormalities (Gelb et al. 1999). These symptoms are caused by the depletion of dopamine (DA) in the target structures of nigral DA neurons, whose progressive degeneration represents the pathological hallmark of PD (Dauer and Przedborski 2003; Fahn 2003). Positron emission tomography (PET) studies in human patients have shown that the severity of Parkinson-ian motor symptoms is inversely related to the levels of 18F-fluorodopa (FD) uptake in the motor part of the striatum, that is, the putamen (Morrish et al. 1996; Brooks 2003).
The motor symptoms of PD may be accompanied by autonomic disturbances affecting the cardiovascular system, gastrointestinal and urinary tracts, as well as sweat and thermoregulation (Jost 1995; Schrag et al. 2000). Moreover, PD patients show a high incidence of depression and cognitive impairment (Brown and Marsden 1984; Schrag et al. 2000). These non-motor symptoms are related to the degeneration of brain structures other than the nigrostriatal DA neurons
(Ito et al. 2002; Brooks 2003). Although neuronal loss is massive in the substantia nigra pars compacta (SNpc), the neurodegenerative process in PD involves some additional brain stem structures, such as the locus ceruleus, the dorsal nucleus of the vagus nerve, and the reticular formation in the pons and the midbrain (Duyckaerts et al. 2003; Mayer 2003). Neurodegeneration may also be pronounced in the cortex and basal forebrain, accounting for the high liability to cognitive decline in PD patients (Girotti and Soliveri 2003; Kovari et al. 2003). The motor symptoms of PD represent a major source of disability for the vast majority of patients (Schrag et al. 2000), calling for DA replacement therapy early on during the course of the disease.
Was this article helpful?