Trisomy 21 or Down syndrome (DS) is a genetic disorder characterized by an extra copy of chromosome 21, which leads to the dysfunction of several metabolic pathways. In Down syndrome, oxidative stress is associated with neurodevelopmental abnormalitiesto a neuronal dysfunction and the appearance of a dementia resembling Alzheimer’s disease. In addition, chronic oxidative stress increases the risk of cardiovascular diseases and of certain cancers in this group of patients.
The studycarried out on the mouse model of Down syndrome, focused on the impact of aging on oxidative stress and liver fibrosis. She notes that:
- mouse models exhibit increased levels of hepatic oxidative stress and impaired antioxidant defenses, reduced glutathione levels, and increased lipid peroxidation;
- their liver presents chronic inflammation, altered mitochondria (cell energy plants), dysregulated lipid metabolism, all favoring the development of non-alcoholic fatty liver disease;
- their liver thus presents an increase in fibrosis which is predictive of a progression towards liver cirrhosis ;
- taken together these results confirm
the increased risk with age of liver pathologies in people with Down syndrome.
These observations highlight the role of the liver in these pathologies associated with Down’s syndrome.
With hope for a therapeutic strategy using antioxidants, targeting oxidative stress and lipid metabolism, and making it possible to prevent or attenuate these complications in this group of patients.
The proof of concept of this therapeutic avenue is in fact provided here… in mice.
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