There is an increasing body of evidence suggesting the involvement of long non-coding RNAs (lncRNAs) in neural development and function. Nevertheless, the relationship between lncRNAs and Alzheimer’s disease (AD) remains uncertain. Previous genome-wide association studies (GWAS) have linked cancer susceptibility candidate 15 (CASC15) with AD. This study aims to comprehensively investigate the characteristics and mechanisms underlying CASC15-mediated synaptic plasticity in hippocampal neurons through the FMR1-NTF3 axis.
Abstract:
Alzheimer’s disease (AD) is a debilitating systemic disorder that has a detrimental impact on the overall well-being of individuals. Emerging research suggests that long non-coding RNAs play a role in neural development and function. Nevertheless, the precise relationship between lncRNAs and Alzheimer’s disease remains uncertain. The authors’ recent discoveries have uncovered an unconventional mechanism involving the regulation of synaptic plasticity and the functioning of the hippocampal fragile X mental retardation protein 1 (FMR1)—neurotrophin 3 (NTF3) pathway, which is mediated by cancer susceptibility candidate 15 (CASC15). Subsequently, functional rescue experiments were performed to illustrate the efficient delivery of exosomes harboring a significant amount of 2610307p16Rik transcripts, which is the murine equivalent of human CASC15, to the hippocampal region of mice. This resulted in significant improvements in synaptic morphological plasticity and cognitive function in APP/PS1 mice. Given the pivotal involvement of CASC15 in synaptic plasticity and the distinctive regulatory mechanisms of the CASC15-FMR1-NTF3 axis, CASC15 emerges as a promising biomarker for Alzheimer’s disease and may even possess potential as a feasible therapeutic target.
Author list:
Yuankang Zou†, Bo Gao†, Jiaqiao Lu†, Keying Zhang†, Maodeng Zhai, Ziyan Yuan, Michael Aschner, Jingyuan Chen, Wenjing Luo*, Lei Wang*, Jianbin Zhang*
How to cite:
Y. Zou, B. Gao, J. Lu, K. Zhang, M. Zhai, Z. Yuan, M. Aschner, J. Chen, W. Luo, L. Wang, J. Zhang, Exploration 2024, 20230154.
https://doi.org/10.1002/EXP.20230154