ABSTRACT

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects 1% of the population above the age of 60. The cause of the disease remains unknown. The histopathological hallmark of the disease is a loss of dopaminergic neurons in the substantia nigra pars compacta (SN) resulting in the loss of striatal dopamine (DA) and the presence of intracytoplasmic Lewy body inclusions. The loss of striatal DA causes the cardinal parkinsonian signs of rest tremor, rigidity, postural instability, and bradykinesia. As the disease progresses, motor dysfunction worsens overtime and additional incapacitating features appear. Since patients with PD have a normal life span, they must endure crippling symptoms for many years, severely impacting their quality of life. Pharmacological treatment options for PD are often limited by the ability of prodopaminergic drugs to function within the nigrostriatal system, without activating other dopaminergic, but nonnigrostriatal, regions of the central nervous system (CNS). Even if that obstacle is overcome, considerations regarding the chronic availability of the drug can limit drug utility.