Current and potential treatments of Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive, degenerative neurological disorder characterized by rest tremor, bradykinesia, cogwheel rigidity and postural instability (Lang & Lozano, 1998). In the later stages of the illness approximately 30–40% of patients will develop cognitive compromise. The cardinal pathological features of PD are loss of neurons on the substantia nigra pars compacta (SNpc) and the presence of eosinophilic, intracytoplasmic inclusions, and Lewy bodies (Braak & Braak, 2000). The neurons of the SNpc project primarily to the caudate and putamen, which are referred to collectively as the striatum, and utilize the neurotransmitter dopamine. Dopamine is severely reduced in the SNpc and striatum in parkinsonian brains (Hornykiewicz, 2002). Although the loss of neurons is most conspicuous in the SNpc, neuronal loss and Lewy bodies are found in a number of brain regions, e.g. locus ceruleus, entorhinal region and amygdala (Braak & Braak, 2000). The neuronal loss and the presence of Lewy bodies in regions other than the SNpc suggest that although treatments that target only the nigrostriatal dopaminergic system may substantially benefit patients, they are unlikely to completely resolve the deficits of PD. The following review presents a strategic framework through which to consider targets for therapies of PD. In some of the areas we are just beginning to have treatments, e.g. slowing the progression of the disease, and in others we have well-established therapies, e.g. augmentation of the function of the remaining dopaminergic system.