Pathological considerations in the treatment of Parkinson's disease: more than just a wiring diagram

Parkinson's disease (PD) represents a common but challenging condition in which an increasing number of therapeutic options have evolved over the course of the last 50 years. The introduction of dopaminergic therapies has dramatically improved outcomes but life expectancies remain significantly curtailed. Currently, all available treatment options are directed towards the amelioration of symptoms. However, it is hoped that a greater understanding of the distinctive pathology underlying PD might offer some novel therapeutic approaches. The identification of degeneration within the nigrostriatal tract as the most prominent pathological process in PD has led to the development of a number of therapies. However, despite initially good symptomatic control it has become clear that the longer-term use of these medications is associated with a number of debilitating motor complications. The management of these drug-related issues has necessitated a further tier of therapeutic options based largely on a greater understanding of the basal ganglia circuitry involved. Indeed, surgical interventions targeting these neural circuits have provided increased control of motor symptoms in patients with advanced disease, however, such techniques still fail to slow or reverse the disease. To this end, a number of novel approaches focussed on restoration or repair of the diseased brain have received increasing attention. Nevertheless, there are multiple symptoms that are unresponsive to any of these therapies, highlighting the involvement of other neurotransmitter systems and the complexities of the disease beyond the basal ganglia circuitry. An appreciation of the ongoing neurodegenerative processes at the core of PD and the burden of disease associated with them, emphasises the need for increased research into more effective and comprehensive treatment methodologies.