Study: “Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer’s disease and aging”
Publisher: Nature
Published date: January 2024
PubMed link to study: https://pubmed.ncbi.nlm.nih.gov/38238311/
Recent research has revealed a cellular process known as Death Induced by Survival gene Elimination (DISE), which plays a significant role in the progression of Alzheimer’s disease and aging. This study explores how the DISE mechanism correlates with neurotoxicity in Alzheimer’s disease and aging, offering potential new directions for treatment strategies.
Feel welcome to share your own thoughts on this research in the comment section below as well. I will be happy to discuss and learn more about how you see its potential in this field.
Summary of Key Findings
- DISE Mechanism: Small RNAs involved in DISE target essential survival genes to induce cell death, particularly in the context of AD, where it is associated with amyloid-beta (Aβ42) toxicity.
- Genetic Regulation: The study finds that in AD and aging brains, there is an increased presence of toxic RNAs that enhance DISE activity. Conversely, brains of individuals termed “SuperAgers” exhibit RNA profiles that are less prone to induce DISE, suggesting a protective mechanism against neurodegeneration.
- Therapeutic Potential: Modulating the balance of toxic and non-toxic RNAs in the brain could offer a method to combat neurodegenerative changes associated with aging and Alzheimer’s disease.
Detailed Exploration of DISE in Aging and Alzheimer’s Disease
The concept of DISE involves a subtype of RNA interference where specific short RNAs target and silence genes critical for cell survival, initiating programmed cell death. This study extends our understanding of DISE by linking it to the neurotoxic effects of amyloid-beta oligomers in Alzheimer’s disease, as well as to broader processes of aging.
In Alzheimer’s disease models, including those based on mouse studies and induced pluripotent stem cell-derived neurons from AD patients, researchers have observed an increase in the proportion of toxic RNA sequences that activate DISE. These sequences contribute to the cellular damage and neurodegeneration characteristic of AD.
In contrast, analysis of brain samples from SuperAgers—older adults who maintain exceptional cognitive function—shows a different pattern. These individuals have a higher prevalence of non-toxic RNA sequences, which seem to confer resistance to the cell death typically seen in normal aging and Alzheimer’s disease.
Implications for Treatment and Longevity
This correlation between RNA profiles and cell survival suggests new avenues for therapeutic development. By enhancing the brain’s repertoire of non-toxic RNAs or by developing molecules that can inhibit the action of toxic RNAs, it may be possible to mitigate the cellular mechanisms that lead to neurodegeneration.
Such interventions could theoretically extend the period of cognitive health in the elderly, potentially delaying or reducing the incidence of Alzheimer’s disease. Moreover, understanding and manipulating DISE could also contribute to broader anti-aging strategies by preserving cell function in various tissues of the body.
It will be interesting to follow any further research based on this study, and especially if studies will be conducted on more advanced animal models or even human trials to provide even better insights.
In Summary
This study on DISE offers important insights into the genetic and molecular underpinnings of Alzheimer’s disease and aging. By targeting the RNA mechanisms that induce cell death, researchers are uncovering potential strategies to combat neurodegenerative diseases and promote healthier aging, thus opening up promising paths for future research and therapy development in gerontology and neurology.
