Oxidative stress could potentially be a significant factor in the manifestation of Alzheimer's symptoms, according to initial research.

Angelman syndrome (AS), a condition caused by the loss or malfunction of the maternally inherited UBE3A gene, has long been a mystery in the medical community. However, a recent study published in Molecular Psychiatry has shed new light on the role of oxidative stress and mitochondrial dysfunction in AS.

The study, led by a team of researchers, aimed to broaden the understanding of AS within the Angelman community. They observed significant changes in developing nerve cells taken from mouse embryos with AS-like disease, but not their healthy counterparts. These changes included alterations in mitochondrial function consistent with vulnerability to cell death and enhanced mitochondrial ROS production.

The UBE3A enzyme, critical in certain areas of the brain, is responsible for symptoms such as severe neurological symptoms, behavioral changes, and intellectual and physical disabilities that characterise AS. The study found that a UBE3A deficiency affects the function of mitochondria, leading to oxidative stress in certain parts of the brain.

The UBE3A gene, deficient in Angelman syndrome, is involved in regulating cellular stress responses, including endoplasmic reticulum stress and protein folding during early brain development. This suggests that UBE3A dysfunction could contribute to the oxidative stress imbalance in the developing brain of people with AS.

The team also found that AS cells had low levels of glutathione, a molecule that helps defend mitochondria against oxidative environments. Depleting glutathione led to significant increases in cell death, supporting its role in AS cells' vulnerability to apoptosis. Treatment with glutathione, which naturally fights oxidative stress, was able to reverse some of these abnormalities in the study.

However, supplementing cells with glutathione only reduced ROS levels and the rate of apoptosis to some extent. Some mitochondrial alterations remained, indicating that while glutathione plays a crucial role in mitigating oxidative stress, it may not be the sole solution to the problem.

The findings suggest that oxidative stress and mitochondrial dysfunction may play a key role in driving AS symptoms via an altered susceptibility to apoptosis. This knowledge will pave the way toward novel therapeutic approaches addressing mitochondrial-related anomalies in early brain development, not only for AS but also other neurodevelopmental disorders.

It is important to note that further studies are needed to better understand the relationship between UBE3A and oxidative stress in early AS development. Symptoms of AS can be observed in children as young as 6 months old, with most being diagnosed between 9 months and 6 years old.

The study further examined mitochondrial function and ROS levels during early AS brain development. The findings underscore the importance of continued research into the underlying mechanisms of AS to develop effective treatments and improve the quality of life for those affected by this condition.

Oxidative stress could potentially be a significant factor in the manifestation of Alzheimer's symptoms, according to initial research.