Parkinson's disease is probably not one disease but several with common clinical, pathological, and, possibly, biochemical end points. Although the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the only environmental agent identified so far that is known to be capable of causing parkinsonism (and has done so within 14 days of exposure), other environmental factors such as use of pesticides and herbicides have been linked with an increased risk of disease. There is increasing
evidence for a genetic component in the cause of
Parkinson's disease.Biochemical abnormalities have been identified in the affected brain region in Parkinson's disease that provide clues to how genetic or environmental factors may induce cell death. There is much evidence of increased oxidative stress and free radical damage in the substantia nigra. There is also evidence for a defect of mitochondrial energy production. Other studies have shown that there may be abnormal calcium handling in dopaminergic neurones and that the gliosis that accompanies nigral cell death may also have a inflammatory component.With the exception of fetal nigral implants, all
treatment currently
available for Parkinson's disease is only symptomatic. Levodopa is the most commonly used treatment for Parkinson's disease. The development of motor complications with levodopa limits its general usefulness. Direct acting
dopamine agonists have been available for some years, but some evidence suggests that those developed more recently have better efficacy and are associated with fewer side effects. Antimuscarinic
drugs and amantadine remain viable alternatives to dopamine related drugs, although their use is often limited by side effects and tolerance. The first priority is to maximise the efficacy and safety of the
treatments currently available. The frequency of complications encountered with levadopa is substantially less with dopamine agonists. Thus, there is a strong argument for starting symptomatic treatment of Parkinson's disease with a dopamine agonist. Drugs with new forms of action, such as dopamine reuptake inhibitors and adenosine antagonists, have proved promising in animal and early clinical studies. Adenosine A2A receptors are present in high concentration in the striatum the area to which the dopaminergic neurones of the substantia nigra project. Thus, adenosine A2A antagonists may present a new treatment for Parkinson's disease. Neurorescue could be considered a mechanism to reverse established metabolic abnormalities and restore normal neuronal function and survival. Clinically, this would result in an improvement in symptoms as well as a halt in the progress of the disease.. The development of such treatments is obviously limited by our knowledge of the biochemical events that cause cell death; at present only a few candidate treatments are available.