By DAVID POGUETIANIC and MARK ROGERSMANENIC, Associated PressA key feature of neurodegenerative diseases is that they can be caused by the accumulation of genetic material, such as DNA.
Scientists at the Institute for Molecular Neurobiology and Therapeutics (IMNT) in Barcelona, Spain, have found that such a mechanism can be triggered by stress in mice.
This discovery could help elucidate how stress triggers the expression of genes in the brain, and may pave the way for developing drugs that target the same stressor in humans.
In a study published in the journal Science, the researchers used a mouse model of AD that includes the gene for a protein called APOE-3, which encodes a protein that promotes cell survival in the case of stress.
When the researchers introduced a high-calorie diet into the mice, APOE3 activity decreased.
After a week, the mice showed signs of stress-induced memory impairment, such that the mice would not eat.
But after they were allowed to feed, APO3 activity returned to normal levels, indicating that stress had no effect on APOE2.
The researchers believe the findings are the first evidence that stress-driven loss of memory in AD could be triggered in a mouse by stress-like stimuli, and that APOE4 could be the mechanism.
The scientists then tested whether the mice could use stress to restore memory to normal.
They found that mice with low levels of APOE1 and APOE5 activity exhibited memory impairments and also had reduced levels of APP1 in the hippocampus, a brain region crucial for learning and memory.
The researchers also found that these mice were more likely to develop the AD-like behavior of “inappropriate eating,” in which they ate too much, and were less likely to show symptoms of AD symptoms, such a lethargy, lethargic behavior and memory loss.
In addition, the APOE protein appears to be involved in AD-related behavior, with some studies suggesting that APO1, which normally regulates the immune system, may also be involved.
“It’s clear that APoE1 is important for AD, and we want to know if this is a mechanism by which APo1 promotes stress,” says Dr. José Luis García-Cordón, a member of the IMNT team and first author of the study.
“We think it could also play a role in AD.
This could be a way to help our understanding of AD.”
In a related study, researchers from the Universidad Autonoma de Barcelona and the University of Barcelona discovered that APOA, the gene that encodes APOE, is critical for AD.
They then found that when the mice were given a high calorie diet, the levels of protein in the mice’ brains increased.
APOA protein also appears to play a key role in the process of AD.
This work also has implications for the treatment of AD patients, which are often treated with drugs that have anti-inflammatory properties.
The team is now working on using APOE as an anti-inflammatory agent in the clinic, and is exploring the potential of APOA to prevent AD-associated memory loss in the future.
The team is also investigating the effects of a neuro-protective peptide, which could potentially protect against the neurotoxic effects of stress in AD patients.
“We have shown that APOB is required for stress-dependent memory loss, and therefore it is possible that APob may also play an important role in stress-associated brain damage,” says Professor Roberto M. Martínez, who led the study and is now at the University College London.
“The findings of this study also indicate that APobe is a protein critical for stress tolerance in the context of AD, so it could have a role to play in the management of AD as a whole.”