1 Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong 637100, China
2 School of Clinical Medicine, North Sichuan Medical College, Nanchong 637100, China
3 Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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.
Keywords
Alzheimer’s disease; Lamr1-ps1; Pseudogene; LncRNA; Learning and memory; MiR29c-3p
