Dopaminergic systems and parkinson's disease: Some latest developments in pathogenetic, diagnostic and pharmacotherapeutic investigations

Abstract

Patients suffering from Parkinson's disease (PD) display severe and progressive deficits in motor behavior, predominantly as a consequence of the degeneration of dopaminergic neurons, located in the mesencephalon and projecting to striatal regions. The cause of PD is still an enigma. In general, pharmacotherapy comprises symptomatic treatment with dopaminergic compounds, which induce a dramatic initial improvement, although serious problems gradually develop after longterm treatment. This paper describes some recent investigations in pathogenetic, diagnostic and pharmacotherapeutic mechanisms related to dopaminergic systems and PD, as they have been performed in our group. — Pathogenetic mechanisms will be highlighted along the line of the oxidative stress hypothesis and especially the role of glutathione will be discussed in this respect. Strong indications exist that a decrease in mesencephalic glutathione precedes the dopamine depletion in this brain region of PD patients. — By using iodinated radioligands, selective for dopamine transporters, it is possible now to visualize the degeneration of the dopaminergic neurons with SPECT in the living patient. This creates the possibility to follow the degeneration rate of the dopaminergic neurons and to monitor eventually therapeutic effects of neuroprotective agents in longitudinal studies. — Sofar, the dopaminergic drugs used for the pharmacotherapy of PD have mainly been confined to L‐DOPA and D2 receptor agonists. It will be demonstrated, especially from studies performed in MPTP‐lesioned monkeys, that some recently developed D1 receptor agonists are able to induce dramatic improvements in this animal model.

Beneficial Effect of Vitamin E in Rotenone Induced Model of PD: Behavioural, Neurochemical and Biochemical Study

“…Moreover in clinical trials, it has been seen that the vitamin E therapy has retarded the progression of degenerative process in PD patients [40, 41]. Vitamin E given with rotenone attenuated the rotenone-induced oxidative stress [42] and exhibits a dose dependent effect in PD patients [14]. Also, it has been reported that the levels of glutathione and vitamin E increased in the brain of patients with PD as a compensatory mechanism to deal with oxidative stress [41-43].…”

“…Vitamin E by virtue of its free radical scavenging ability efficiently reduced rotenone induced lipid peroxidation and ROS generated oxidative stress. Also, with vitmain E supplementation there is lesser utilisation of GSH and SOD or we can say that vitamin E replaced the protective enzymes and mechanisms that are deficient in nigral neurons thus sparing the scavenging systems i.e SOD and GSH from the injurious effects of neurotoxins like rotenone and 6-OHDA [40-42]. Thus, providing protection to the antioxidant defense system in dopaminergic neurons hence, lesser DA-nergic neurodegeneration [65].…”