Long non‐coding RNA CASC15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neurons

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 lncRN...

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Main Authors: Yuankang Zou, Bo Gao, Jiaqiao Lu, Keying Zhang, Maodeng Zhai, Ziyan Yuan, Michael Aschner, Jingyuan Chen, Wenjing Luo, Lei Wang, Jianbin Zhang
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Exploration
Subjects:
Online Access:https://doi.org/10.1002/EXP.20230154
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author Yuankang Zou
Bo Gao
Jiaqiao Lu
Keying Zhang
Maodeng Zhai
Ziyan Yuan
Michael Aschner
Jingyuan Chen
Wenjing Luo
Lei Wang
Jianbin Zhang
author_facet Yuankang Zou
Bo Gao
Jiaqiao Lu
Keying Zhang
Maodeng Zhai
Ziyan Yuan
Michael Aschner
Jingyuan Chen
Wenjing Luo
Lei Wang
Jianbin Zhang
author_sort Yuankang Zou
collection DOAJ
description 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.
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spelling doaj-art-523644979f914855a7f566fa9e4adc4e2025-08-20T01:58:08ZengWileyExploration2766-85092766-20982024-12-0146n/an/a10.1002/EXP.20230154Long non‐coding RNA CASC15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neuronsYuankang Zou0Bo Gao1Jiaqiao Lu2Keying Zhang3Maodeng Zhai4Ziyan Yuan5Michael Aschner6Jingyuan Chen7Wenjing Luo8Lei Wang9Jianbin Zhang10Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health Fourth Military Medical University Xi'an ChinaInstitute of Orthopaedic SurgeryXijing HospitalFourth Military Medical UniversityXi'an ChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health Fourth Military Medical University Xi'an ChinaDepartment of UrologyXijing HospitalFourth Military Medical UniversityXi'an ChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health Fourth Military Medical University Xi'an ChinaInstitute of Medical Information and LibraryChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChinaDepartment of Molecular PharmacologyAlbert Einstein College of MedicineBronxNew YorkUSADepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health Fourth Military Medical University Xi'an ChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health Fourth Military Medical University Xi'an ChinaDepartment of Medical Research Center, Clinical Medical CollegeYangzhou UniversityYangzhouChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health Fourth Military Medical University Xi'an ChinaAbstract 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.https://doi.org/10.1002/EXP.20230154Alzheimer's diseaseCASC15FMR1long noncoding RNANTF3synaptic plasticity
spellingShingle Yuankang Zou
Bo Gao
Jiaqiao Lu
Keying Zhang
Maodeng Zhai
Ziyan Yuan
Michael Aschner
Jingyuan Chen
Wenjing Luo
Lei Wang
Jianbin Zhang
Long non‐coding RNA CASC15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neurons
Exploration
Alzheimer's disease
CASC15
FMR1
long noncoding RNA
NTF3
synaptic plasticity
title Long non‐coding RNA CASC15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neurons
title_full Long non‐coding RNA CASC15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neurons
title_fullStr Long non‐coding RNA CASC15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neurons
title_full_unstemmed Long non‐coding RNA CASC15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neurons
title_short Long non‐coding RNA CASC15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neurons
title_sort long non coding rna casc15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neurons
topic Alzheimer's disease
CASC15
FMR1
long noncoding RNA
NTF3
synaptic plasticity
url https://doi.org/10.1002/EXP.20230154
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