How do "PNAS" dangerous genes change the neuroprotective mechanism?

The brain has a natural protective mechanism against Alzheimer’s disease.

The team revealed evidence supporting reactive oxygen species (ROS), which is a natural by-product of cell metabolism, is related to inflammation and other processes, and is a key factor leading to the destruction of neuroprotective mechanisms

In short, these findings provide a new mechanism for the development of Alzheimer's disease and support the idea that a combination of genetic and other cellular changes can induce this disease

When neurons face high levels of reactive oxygen species, neuroprotective mechanisms begin to work, and reactive oxygen species stimulate neurons to produce rich lipids

Previous studies have shown that two brain cell types, neurons and glial cells, work together to prevent neurodegeneration

In previous studies, the researchers linked the neuroprotective mechanism to the strongest genetic risk factor for Alzheimer's disease, the apolipoprotein APOE4

Hugo Bellen, Professor of Special Services in Molecular and Human Genetics at Baylor University, said: "We found that APOE4 is actually unable to transfer lipids to glial cells, while the other two forms of APOE, APOE2 and APOE3, can effectively transfer

"In the current work, we want to identify genes that are essential for lipid droplet formation, especially those that are required for the export of lipids from neurons and the introduction of lipids into glial

The team studied the effects of these Alzheimer's disease risk genes on a fruit fly model, studying only one gene at a time

First author Dr.

In this way, the team demonstrated that several genes related to the risk of Alzheimer’s disease in the whole-genome sequencing study disrupted the formation of neuroprotective lipid droplets, which provided a mechanism that could explain the risks associated with these genes.

In addition, in the Drosophila model, Moulton and his colleagues tested whether the ABCA1 agonist can enable APOE4 in the Drosophila model to mediate the formation of lipid droplets in glial cells

The researchers also studied whether ROS can exacerbate the effects of amyloid on the disease

"As we age, the ROS in the brain will increase

Magazine

Proceedings of the National Academy of Sciences

DOI

10.