There is currently no effective pharmacological therapy to improve the cognitive dysfunction of individuals with Down syndrome (DS). Due to the overexpression of several chromosome 21 genes, cellular and systemic oxidative stress (OS) is one of the most important neuropathological processes that contributes to the cognitive deficits and multiple neuronal alterations in DS. In this condition, OS is an early event that negatively affects brain development, which is also aggravated in later life stages, contributing to neurodegeneration, accelerated aging, and the development of Alzheimer’s disease neuropathology. Thus, therapeutic interventions that reduce OS have been proposed as a promising strategy to avoid neurodegeneration and to improve cognition in DS patients. Several antioxidant molecules have been proven to be effective in preclinical studies; however, clinical trials have failed to show evidence of the efficacy of different antioxidants to improve cognitive deficits in individuals with DS. In this review we summarize preclinical studies of cell cultures and mouse models, as well as clinical studies in which the effect of therapies which reduce oxidative stress and mitochondrial alterations on the cognitive dysfunction associated with DS have been assessed.
Melatonin is a molecule with numerous properties, which are applicable to the treatment of different types of cancers. Experimental in vitro and in vivo studies conducted with human cancer cells or animal models of carcinogenesis, have shown that melatonin enhances apoptosis and inhibits cell proliferation of several human cancer cells, reduces tumor growth rate and its metastases, reduces the side effects of chemotherapy and radiotherapy, decreases the resistance to standard cancer treatments, and potentiates the therapeutic effects of other conventional therapies. These satisfactory results obtained from “bench” need to be studied in clinical trials to verify whether they are applicable to “bedside”. In this article we review the clinical trials carried out in the last 25 years which are focused on the therapeutic use of melatonin in cancer treatment. We conclude that melatonin is an effective adjuvant drug to practically any conventional cancer therapy since it is capable of improving the quality of life of patients, by normalizing sleep and alleviating general symptoms associated with tumor disease and treatment such as pain, asthenia, anorexia, etc. In the particular case of hormone-dependent breast cancer, melatonin's antiestrogenic properties make this indoleamine ideally suited for use in association with other synthetic anti-estrogen agents, as melatonin increases their efficacy while reducing their undesirable effects. Furthermore, melatonin could be an appropriate co-treatment for preventive treatment of breast cancer in people with elevated risk for this kind of neoplasia.
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