Toxic RNA strands known to cause cells to self-destruct have been discovered in both Alzheimer’s disease and the aging brain, suggesting new approaches to treating neurodegenerative diseases such as dementia. ing.
In a mouse and human brain-based study led by Northwestern University in the US, researchers identified short RNAs (ribonucleic acid) is associated with DNA damage and cell death associated with disease and related factors.
They also found that protective short RNAs in the brain decrease with age, which can lead to the progression of Alzheimer’s disease, and that people over 80 with excellent memory (‘super-agers’) ) also found higher levels of protective short RNA.
“We found that in aging brain cells, the balance between toxic and protective short RNAs shifts toward toxic short RNAs.” To tell Northwestern University biochemist Marcus Peter, lead author of the study.
about One in nine U.S. adults is over 65 years old Alzheimer’s disease is a disease characterized by the development of amyloid-beta plaques, tau tangles, and brain cell death. It has been difficult to identify the sequence of events that lead to excessive brain cell death and dysregulation.
There are drugs that can slow the progression of Alzheimer’s disease, but the search for more effective options continues. The study authors believe that targeting the RNA strand could open up new therapeutic pathways.
“The overwhelming investment in Alzheimer’s disease drug discovery has focused on two mechanisms,” Peter says. explain“It reduces amyloid plaque burden in the brain (which is a hallmark of Alzheimer’s disease diagnosis and takes up 70 to 80 percent of the effort) and prevents tau phosphorylation and tangles.”
Peter et al. used a variety of methods, including mouse models of Alzheimer’s disease, mouse brains, “super-ager” brains, neurons isolated from healthy and Alzheimer’s patient stem cells, and cell lines derived from human brains. We investigated the behavior of RNA.
RNA carries genetic information from DNA to parts of the cell, translates genetic recipes, and produces proteins essential for various cellular functions. Non-coding short RNAs play a role in regulating gene expression by controlling the proteins encoded by long RNAs. RNA interference.
However, the protective effect of RNA decreases with age and may even be harmful.
The research team discovered that short RNA molecules with specific characteristics can trigger cell death. These toxic short RNAs interfere with the production of essential proteins and can cause symptoms such as: Death caused by removal of survival genes (DSE) is a process that is active in humans and rodents and plays an important role in killing cancer cells.
Patients with Alzheimer’s disease have a lower incidence of cancer, which the researchers speculate may mean that an overactive DISE mechanism also contributes to cell death in Alzheimer’s disease.
They found a correlation between DISE, DNA damage, neuronal cell death and aging in Alzheimer’s disease. Neurons in a mouse model of Alzheimer’s disease, as well as cells derived from Alzheimer’s patients, had reduced levels of specific protective short RNA molecules.
Aging brains also have fewer protective RNA molecules, allowing more toxic short RNAs to invade and carry out RNA interference, whereas superager brains have higher levels.
Experiments on cells exposed to amyloid beta fragments in the laboratory showed increased cell death and DNA damage associated with toxic RNA changes.
Increasing the amount of protective RNA and increasing the activity of the proteins involved appears to provide some protection to cells exposed to amyloid beta and completely prevent the DNA damage also observed in Alzheimer’s patients.
Based on these findings, increasing brain levels of protective RNAs may represent a new strategy for neurodegeneration treatment.
“Our data shed new light on why, in almost all neurodegenerative diseases, affected individuals live symptom-free for decades, then lose cellular protection with age and gradually begin to develop the disease. We provide an explanation,” Peter said. To tell.
“Stabilizing or increasing the amount of protective short RNAs in the brain could represent an entirely new approach to halting or slowing Alzheimer’s disease and neurodegeneration in general.”
This research nature communications.