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6-Hydroxydopamine (6-OHDA) is a dopaminergic neurotoxin putatively involved in the pathogenesis of Parkinson's disease (PD). Its neurotoxicity has been related to the production of reactive oxygen species. In this study we examine the effects of the antioxidants ascorbic acid (AA), glutathione (GSH), cysteine (CySH), and N-acetyl-CySH (NAC) on the(More)
The results of several in vitro studies have shown that cysteine prodrugs, particularly N-acetylcysteine, are effective antioxidants that increase the survival of dopaminergic neurons. N-acetylcysteine can be systemically administered to deliver cysteine to the brain and is of potential use for providing neuroprotection in the treatment of Parkinson's(More)
It is now established that the brain possesses a local renin-angiotensin system and that angiotensin II exerts multiple actions in the nervous system, including regulation of striatal dopamine release. Furthermore, angiotensin activates NADPH-dependent oxidases, which are a major source of superoxide, and angiotensin-converting enzyme inhibitors, commonly(More)
1,2,3,4-Tetrahydroisoquinoline (TIQ) and 1,2,3,4-tetrahydro-beta-carboline (THbetaC) are two endogenous or exogenous dopaminergic proneurotoxicants supposedly involved in the etiology of Parkinson's disease. We investigated whether the chronic administration of a twice daily dose of a cigarette smoke solution might modify the endogenous concentrations of(More)
There is growing evidence indicating that oxidative stress is a key contributor to the pathogenesis and progression of Parkinson's disease. The brain, and particularly the basal ganglia, possesses a local rennin-angiotensin system. Angiotensin activates NAD(P)H-dependent oxidases, which are a major intracellular source of superoxide, and angiotensin(More)
The relation between changes in the concentrations of some of the neuroactive extracellular amino acids (glutamate, aspartate, gamma-aminobutyric acid, glycine and taurine) and epileptic seizures has been tested in a new experimental model of seizures induced by picrotoxin microdialysis in chronic freely moving rats. During ictal discharges (paroxysmal(More)
Angiotensin II activates (via type 1 receptors) NAD(P)H-dependent oxidases, which are a major source of superoxide, and is relevant in the pathogenesis of several cardiovascular diseases and certain degenerative changes associated with ageing. Given that there is a brain renin-angiotensin system and that oxidative stress is a key contributor to Parkinson's(More)
1,2,3,4-Tetrahydro-beta-carboline (TH beta C) is an endogenous or environmental neurotoxic factor putatively involved in the development of Parkinson's disease (PD). As part of our efforts to characterize the mechanism of the reported protection of smoking against PD, we have examined the interaction between TH beta C and cigarette smoke. We found that TH(More)
The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer's disease (AD), shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel(More)
The renin-angiotensin system (RAS) was initially considered as a circulating humoral system controlling blood pressure, being kidney the key control organ. In addition to the 'classical' humoral RAS, a second level in RAS, local or tissular RAS, has been identified in a variety of tissues, in which local RAS play a key role in degenerative and aging-related(More)