The role of neurotransmitters and neuropeptides in Parkinson's disease: implications for therapy

Parkinson's disease is a progressive neurodegenerative disease of the basal ganglia. Pathologically, it is characterized by continuous dopaminergic cell loss in the nigrostriatal system. The classic triad of signs comprises resting tremor, rigidity and bradykinesia. The decrease of dopamine content in the substantia nigra pars compacta in Parkinson's disease disrupts the delicate balance between neurotransmitters, e.g., noradrenaline, serotonin (5-HT), acetylcholine, GABA and glutamate, and also neuropeptides, e.g., enkephalins and substance P, in the brain, especially within the basal ganglia circuit. This causes a variety of neurotransmission changes that eventually influence the motor cortex, and as a result affect movement control and autonomic functions. In addition, levodopa and dopamine agonists might also alter mRNA transcripts of neurotransmitters and neuropeptides in the basal ganglia, thus contributing to the imbalance in neurotransmission. An understanding of the complex relationships among neurotransmitters, neuropeptides and their receptors may enable manipulation of the system with new drugs or microsurgical techniques. The aim of these novel therapies would be to reduce the problems associated with levodopa therapy, such as dyskinesias, and to improve the quality of life of Parkinson's patients.