Neurotransmission in Parkinson's disease: beyond dopamine

The pathological mechanism most frequently associated with Parkinson’s disease is the neurodegeneration of dopaminergic neurons of the substantia nigra pars compacta and the subsequent loss of dopaminergic input to the rest of the basal ganglia. This loss of dopamine correlates well with the characteristic motor symptoms, but cannot explain the appearance of a multitude of non-motor symptoms including sleep disturbances, fatigue, apathy, anxiety, olfactory dysfunction, pain, sweating, constipation, depression, cognitive impairment and dementia that can have a considerable impact on patients’ quality of life and may be more debilitating than the motor dysfunction. Since some of these non-motor symptoms occur prior to the appearance of the movement disorders, other neuronal systems must also be involved that rely on neurotransmitters other than dopamine. Moreover, treatments that target only the dopaminergic system are insufficient to alleviate both motor and non-motor symptoms. In this article, Barone focuses on the non-dopaminergic neural systems associated with the non-motor symptoms in Parkinson’s disease, and highlights their potential suitability as therapeutic targets.