Pseudogene Lamr1-ps1 Aggravates Early Spatial Learning Memory Deficits in Alzheimer's Disease Model Mice.
10.1007/s12264-024-01336-6
- Author:
Zhuoze WU
1
;
Xiaojie LIU
1
;
Yuntai WANG
1
;
Zimeng ZENG
1
;
Wei CHEN
1
;
Hao LI
2
Author Information
1. Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, 637100, China.
2. Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. lihaochn@hust.edu.cn.
- Publication Type:Journal Article
- Keywords:
Alzheimer’s disease;
Lamr1-ps1;
Learning and memory;
LncRNA;
MiR-29c-3p;
Pseudogene
- MeSH:
Animals;
Alzheimer Disease/pathology*;
Pseudogenes/genetics*;
Mice;
Memory Disorders/metabolism*;
MicroRNAs/genetics*;
Disease Models, Animal;
Spatial Learning/physiology*;
Mice, Transgenic;
Presenilin-1/genetics*;
Male;
Amyloid Precursor Protein Secretases/metabolism*;
Mice, Inbred C57BL;
Aspartic Acid Endopeptidases/metabolism*
- From:
Neuroscience Bulletin
2025;41(4):600-614
- CountryChina
- Language:English
-
Abstract:
Alzheimer's disease (AD), a neurodegenerative disorder with complex etiologies, manifests through a cascade of pathological changes before clinical symptoms become apparent. Among these early changes, alterations in the expression of non-coding RNAs (ncRNAs) have emerged as pivotal events. In this study, we focused on the aberrant expression of ncRNAs and revealed that Lamr1-ps1, a pseudogene of the laminin receptor, significantly exacerbates early spatial learning and memory deficits in APP/PS1 mice. Through a combination of bioinformatics prediction and experimental validation, we identified the miR-29c/Bace1 pathway as a potential regulatory mechanism by which Lamr1-ps1 influences AD pathology. Importantly, augmenting the miR-29c-3p levels in mice ameliorated memory deficits, underscoring the therapeutic potential of targeting miR-29c-3p in early AD intervention. This study not only provides new insights into the role of pseudogenes in AD but also consolidates a foundational basis for considering miR-29c as a viable therapeutic target, offering a novel avenue for AD research and treatment strategies.
