Parkinson's disease - A review

Abstract

Parkinson's disease is a common neurological condition. Environmental, genetic factors and age are important predisposing factors, but there continues to be increasing evidence for a genetic component. Apoptosis and necrosis have been implicated in the loss of the nigral neurons in patients with parkinson 's disease. Mitochondrial dysfunction, oxidative stress, the actions of excitotoxins, deficient neurotrophic support and immune mechanisms are contributory. Excessive activity of the subthalamic nucleus has also been found to contribute to the symptoms of parkinsons disease using the neurotransmitter glutamate, blockade of which might provide an effective treatment of parkinson's disease. Treatment could be preventive, symptomatic or restorative. Neuroprotective agents prevent apoptosis by upregulating apoptosis defence gene and down regulating apoptosis promoting genes. Selegilline (deprenyl) has selective anti apoptotic properties by increasing mitochondrial energy production and reducing generation of free radicals. Free radical scavengers such as atocopherol, high doses of ascorbate, antioxidants such as selenium and ubiquinone, drugs inhibiting glutamate release or receptor interaction such as N- methyl 4 - valine antagonist and aspirin, which down regulate glutamate receptors have been tried without proven benefit. Non-steroidal anti-inflammatory agents and interferon b have also been tried with no documented efficacy. Except for functional neurosurgical procedures, levodopa remains the most effective replacement therapy for parkinson's disease. Several new methods of therapy are under development, including the inhibition of dopamine catabolism, synthesis of new dopamine receptor agonists, and manipulation of the function of the subthalamic nucleus. However, as new drugs become available, treatments that influence oxidative phosphorylation and damage due to free radicals, excessive iron deposition, disturbances of calcium homeostasis, cytokines, excitotoxicity, nitric oxide, apoptosis, and the products of causative genes may all be considered in attempts to provide effective neural protection. Fetal nigral implants into the striatum improve symptoms while the transplantation of adrenal medulla tissue to the striatum has been largely abandoned because of its lack of efficacy. Allogenic transplantation of fetal mesencephalon is currently been studied, and initial reports show promising results. Also under study are the intraventricular delivery of the dopaminergic neurotrophic factor (GDNF) and the implantation of foreign cells in semi-permeable polymeric capsules, which obviates the need for potentially harmful immunosuppressive therapy. In conclusion, the treatment of parkinson's disease remains enigmatic with high cost of medication and significant morbidity. Till date, surgery has a limited role in the management of parkinson's patients. In the future however, surgical interventions may incorporate advances in gene therapy and genetransfer is being examined in animal models of parkinsonism. Genes coding for molecules that block apoptosis, scavenge free radicals, enhance the clearance of toxic metabolites, or improve mitochondrial function could also be considered.