Year: 2024
Type: article
Abstract: BACKGROUND: Compelling evidence has shown that long non-coding RNAs (lncRNAs) contribute to Alzheimer's disease (AD) pathogenesis including β-amyloid plaque deposition (Aβ) and intracellular neurofibrillary tangles. In this study, we aimed to investigate the critical role of lncRNA Gm20063 in AD. METHOD: Six-month-old male APP/PS1 transgenic mice and wild type (WT) C57BL/6 (B6) littermates were obtained from the Nanjing University Animal Model Research Center. AAV mediated over-expression or knockdown of Gm20063 in hippocampus neurons though stereotactic technique. Behavioral tests were performed to evaluate the cognitive and memory function of APP/PS1. Electrophysiological tests, Golgi staining and Western blotting was applied to determine the synaptic plasticity. The potential targets of Gm20063 were identified by mass spectrometry (MS), RNA-binding protein immunoprecipitation (RIP) and RNA in situ hybridization (RNA scope). RESULT: The expression of Gm20063 was significantly increased in the hippocampus of APP/PS1 mice. Overexpression of Gm20063 ameliorated cognitive decline, reduced Aβ deposition, enhanced synaptic plasticity and Aβ phagocytized by microglia in APP/PS1. In addition, knockdown of Gm20063 accelerated the memory deficits and worsened the AD pahogenesis in APP/PS1 mice. Furthermore, Gm20063 interacted with TDP-43 in the hippocampus, and regulated the post-translational modifications of TDP-43. CONCLUSION: Gm20063 attenuated cognitive decline in AD mice, and targeting Gm20063 might be an effective therapy for AD treatment.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.085039
Institutions: Nanjing Drum Tower Hospital, Nanjing University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
OpenAlex ID: W4406050396