
老化およびアルツハイマー病におけるストレス増加に伴い形成されるRNA G四重鎖構造は、タンパク質の凝集を促進し、神経変性を加速させる可能性がある。


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INTRODUCTION As the world population ages, new molecular targets in aging and Alzheimer’s Disease (AD) are needed to combat the expected influx of new AD cases. Until now, the role of RNA structure in aging and neurodegeneration has largely remained unexplored.

METHODS In this study, we examined human hippocampal postmortem tissue for the formation of RNA G-quadruplexes (rG4s) in aging and AD.

RESULTS We found that rG4 immunostaining strongly increased in the hippocampus with both age and with AD severity. We further found that neurons with accumulation of phospho-tau immunostaining contained rG4s, that rG4 structure can drive tau aggregation, and that rG4 staining density depended on APOE genotype in the human tissue examined.

DISCUSSION Combined with previous studies showing the dependence of rG4 structure on stress and the extreme power of rG4s at oligomerizing proteins, we propose a model of neurodegeneration in which chronic rG4 formation drives proteostasis collapse. We propose that further investigation of RNA structure in neurodegeneration is a critical avenue for future treatments and diagnoses.

### Competing Interest Statement

The authors have declared no competing interest.

A New Role for RNA G-quadruplexes in Aging and Alzheimer’s Disease

rna-g四重鎖構造の老化およびアルツハイマー病における新たな役割


RNA G四重鎖構造の老化およびアルツハイマー病における新たな役割


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RNA G-quadruplexes (rG4s) accumulate in the human hippocampus with age and Alzheimer's disease severity, suggesting a potential role in neurodegeneration, possibly by promoting protein aggregation.


rna-g-quadruplexes-increase-with-age-and-alzheimer-s-disease-severity-in-the-human-hippocampus


RNA G-quadruplexes Increase with Age and Alzheimer's Disease Severity in the Human Hippocampus



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