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Antioxidants in Down Syndrome: From Preclinical Studies to Clinical Trials
Noemí Rueda Revilla1, Carmen Martínez-Cué1
1Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, 39011 Santander, Spain.
Abstract:
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.
Insights
Oxidative stress contributes to cognitive decline in Down syndrome (DS). While antioxidants show promise in preclinical studies, clinical trials have not yet demonstrated their efficacy in improving cognition for individuals with DS.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Down syndrome (DS) is characterized by cognitive dysfunction linked to oxidative stress (OS).
- Overexpression of chromosome 21 genes exacerbates OS, impacting brain development and leading to neurodegeneration and Alzheimer's-like pathology.
- Current pharmacological treatments for cognitive deficits in DS are lacking.
Purpose of the Study:
- To review preclinical and clinical studies on therapies targeting OS and mitochondrial dysfunction in DS.
- To assess the potential of reducing OS as a strategy for neuroprotection and cognitive improvement in DS.
Main Methods:
- Summarized findings from cell culture and mouse models of DS.
- Analyzed clinical trial data evaluating OS-reducing therapies.
- Focused on interventions addressing oxidative stress and mitochondrial alterations.
Main Results:
- Preclinical studies demonstrate antioxidant efficacy in DS models.
- Clinical trials have thus far failed to show significant cognitive benefits from antioxidant therapies in DS patients.
- Mitochondrial alterations are a key feature associated with OS in DS.
Conclusions:
- Therapeutic strategies aimed at reducing oxidative stress are a promising avenue for DS research.
- Further investigation is needed to bridge the gap between preclinical antioxidant efficacy and clinical outcomes in DS.
- Addressing mitochondrial dysfunction alongside OS may offer a more effective therapeutic approach for cognitive deficits in Down syndrome.
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