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INTRODUCTION: The aetiology of the neuronal death which occurs in neurodegenerative diseases is still unknown. These disorders are of insidious onset and follow an inexorable, gradually progressive course. The best known and most frequent are Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). DEVELOPMENT: Advances in molecular genetics and neurobiochemistry towards the understanding of processes involved in cell death, suggest the association of phenomena of excito-toxicity and oxidation damage in the selective degeneration of neuronal populations, characteristic of these disorders. CONCLUSION: The evidence presented here suggests that the species reactive to oxygen (SRO) play a direct part in the aetiology and/or pathogenesis of neurodegenerative disorders, although it is still very difficult to establish whether these reactive species represent the primary etiological factor, or are toxic products secondary to tissue damage.

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INTRODUCTION: Genetic therapy is in itself a new type of treatment, of potential use in many neurological conditions currently considered to be resistant to conventional treatment. Great advances have been made in the construction of vectors of expression and carriers of viral genes, thus work is starting on the characterization of target cells for neuronal genetic therapy. DEVELOPMENT: As a result of advances in this field, two methods of genetic transference have evolved. One, 'in vivo', involves transfection of genetic material by means of chemical or viral agents. The 'ex vivo' variant depends on manipulation of culture cells to subsequently inject them into the host organism with a view to correcting the cell phenotype. Both methods have been used in preliminary experiments designed to test the efficacy of genetic transference for improvement of dysfunction of the nervous system. At the present time there is much experimentation with the use of genetic transference using modified cells to synthetize growth factors or key enzymes of the neurotransmission process in biomodels of Parkinsonism and Alzheimer amongst other conditions. CONCLUSIONS: Genetic therapy, as is shown in this review, has great therapeutic potential for nervous diseases which are very severe and complex. There is certainly a long way to go to perfect these techniques, particularly with regard to biological security and regulation of the element transferred. However, when it is used it will mean a major qualitative change in the treatment of nervous system disorders which are at present a cause of severe handicap and have little chance of treatment.

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INTRODUCTION AND OBJECTIVE: Increased oxidative stress during ageing and the neurodegenerative disorders associated with this has been described. The central nervous system is particularly vulnerable to oxidative damage because of its high energy requirements, high oxygen consumption, high tissue concentration of iron and relatively low levels of some antioxidant systems. Treatment with neurotrophic factors may reverse neurone deterioration and stimulate cholinergic activity in aged rats. It may have a similar neuroprotector effect against damage due to ischaemic reperfusion, hypoglycaemia, inflammation and other pathological conditions involving oxidative stress. In this study we determined some indicators of oxidative stress in rat brains during ageing and evaluated this in response to a plan of treatment with murine nerve growth factor (FCN) for 38 days. MATERIAL AND METHODS: Biochemical techniques were used for determination of oxidative stress indicators. RESULTS AND CONCLUSIONS: We found that with age there was a significant increase in phospholipase A2 and superoxide dysmutase activity and concentration of hipoperoxidases, whilst the concentration of reduced glutathion fell. Catalase activity increased in the hippocampal and striate regions and decreased in the cortex and septal area. There was less oxidative stress in rats treated with FCN. In view of our results, we conclude that the level of oxidative stress increases with ageing, with significant differences between areas of the brain. The region most vulnerable to damage from species reactive to oxygen was the hippocampus, and the protective effect of FCN may be related to potentiation of antioxidant defenses.

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INTRODUCTION AND OBJECTIVE: Several authors have suggested that loss of neuronal trophic support may be an important element in the physiopathology of degenerative conditions of the central nervous system such as Alzheimer's dementia, Parkinson's disease or amyotrophic lateral sclerosis amongst others. In the light of present knowledge, the survival of cholinergic populations of the anterior basal cerebrum, closely involved with cognitive processes of memory and learning, is associated with adequate function of the neural growth factor (NGF). These populations are markedly damaged in Alzheimer's disease, and this has been correlated with the progressive loss of memory and intellectual involvement seen in this disorder. The model used in this study was based on section of the septohippocampal connecting pathways, so that transport of regulatory impulses from the hippocampus to the medial septum was interrupted. This has lethal results for the cholinergic neurons of the latter. We have developed a study designed to characterize the expression of the gene of NGF in different regions of the brain, involved in cholinergic neurotransmission in healthy and in damaged tissue. MATERIAL AND METHODS: We used a molecular hybridization technique with a cDNA catheter complementary to the radio-isotope marked NGF human gene. RESULTS AND CONCLUSIONS: The highest levels of expression were found in the healthy cortex and hippocampus. The reduction in the levels of mRNA of NGF in the damaged hippocampus supports the current thesis which considers synaptic activity to be a major regulator of the synthesis of this molecule in the brain.

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