Blocking Enzymes Reverse Alzheimer’s Memory Loss

Inhibiting certain enzymes involved in abnormal gene transcription may offer a way to restore memory loss associated with Alzheimer’s disease, a new study in mice suggests.

The findings could pave the way toward new treatments for Alzheimer’s disease (AD).

“By treating AD mouse models with a compound to inhibit these enzymes, we were able to normalize gene expression, restore neuronal function, and ameliorate cognitive impairment,” says senior author Zhen Yan, a professor in the department of physiology and biophysics in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo.

Alzheimer’s disease alters the expression of genes in the prefrontal cortex, a key region of the brain controlling cognitive processes and executive functions.

When they focused on gene changes caused by epigenetic processes (those not related to changes in DNA sequences) such as aging, the researchers could reverse elevated levels of harmful genes that cause memory deficits in AD.

The current research extends the work the team reported in 2019 in the journal Brain, in which they reversed the loss or downregulation of genes beneficial to cognitive function in AD.

In the new paper in Science Advances, the team reports they reversed the upregulation of genes involved in impairing cognitive function.

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Genetic Test To Detect Earlier Alzheimer’s

A new study published in the journal Epigenetics in February 2020 reports that changes in the methylation status of the Presenilin 1 (PSEN1) gene could help diagnose Alzheimer’s disease (AD) earlier. This study shows for the first time that methylation of this gene is a common feature in AD.

AD is a widespread dementia disorder, involving the loss of cognitive skills such as thinking, making decisions, remembering things in connection, and learning. It affects almost 50 million people the world over, mostly over the age of 60 years but a significant percentage at ages below 50 years. Furthermore, this is only a fourth of all cases, because most patients go undiagnosed.

 

The progressive and incurable nature of this disorder makes it difficult to bear for both the patient and the caregivers. The disease inevitably progresses to the point where complete care is required. Currently, available medications must be given early to have the highest odds of successfully delaying the onset of severe cognitive loss.

The PSEN1 gene is part of a protease complex that catalyzes a process called regulated intramembrane proteolysis. It is important in AD because it is responsible for cleaving the beta-amyloid fragment from the parent AβPP molecule. It is one of several polymorphic genes that regulate normal embryonic regulation but also promote the risk of AD.

Epigenetic modification is an important way to regulate gene activity in the body and can be triggered by environmental factors, including specific lifestyle and nutritional factors. The addition of methyl groups to the DNA (mostly to the cytosine) outside the actual genetic code, called methylation, is a well-known epigenetic modification. Methylation is typically a method to silence or downregulate the associated gene.

Earlier animal studies have shown that the PSEN1 gene can be downregulated, causing a condition very like AD.  However, little research has been done epigenetic modification of the human PSEN1 gene. It is established that people with AD already show altered PSEN1 behavior. The current study is the first to record the frequent occurrence of DNA methylation at this gene in humans with AD.

Source: https://www.news-medical.net/