Overexpression of SFPQ Improves Cognition and Memory in AD Mice

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with multifaceted pathogenesis, which has been extensively investigated, yet effective treatments remain lacking. Splicing factor proline and glutamine rich (SFPQ) is known to play a crucial role in neurodegenerative diseases, includin...

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Main Authors: Jinshan Tie, Hongxiang Wu, Wei Liu, Yuying Li, Lu Li, Suju Zhao, Zhijiao Yuan, Khan Mahmood, Shaochun Chen, Huidong Wu
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/np/3934591
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author Jinshan Tie
Hongxiang Wu
Wei Liu
Yuying Li
Lu Li
Suju Zhao
Zhijiao Yuan
Khan Mahmood
Shaochun Chen
Huidong Wu
author_facet Jinshan Tie
Hongxiang Wu
Wei Liu
Yuying Li
Lu Li
Suju Zhao
Zhijiao Yuan
Khan Mahmood
Shaochun Chen
Huidong Wu
author_sort Jinshan Tie
collection DOAJ
description Alzheimer’s disease (AD) is a complex neurodegenerative disorder with multifaceted pathogenesis, which has been extensively investigated, yet effective treatments remain lacking. Splicing factor proline and glutamine rich (SFPQ) is known to play a crucial role in neurodegenerative diseases, including antioxidant-related functions and regulating gene expression within brain neurons. However, the specific role of SFPQ in AD pathology is not well understood. In this study, an AD mouse model was established through lateral ventricular injection of amyloid-beta1–42 (Aβ1–42). Subsequently, adeno-associated virus was administered to overexpress SFPQ in the hippocampus of AD mice. The results demonstrate that SFPQ overexpression improves recognition and memory in AD mice, while reducing AD-related marker proteins such as amyloid precursor protein (APP) and Tau. Additionally, synaptic and memory-associated proteins, as well as antioxidant proteins like glutathione S-transferase (GST) and heme oxygenase-1 (HO-1), were upregulated. The ratio of antiapoptotic protein Bcl-2 to proapoptotic protein Bax also increased. Furthermore, phosphorylated phosphoinositide 3-kinase (p-PI3K)/PI3K and phosphorylated protein kinase B (p-AKT)/AKT ratios were elevated, indicating activation of the PI3K/AKT signaling pathway. These findings suggest that SFPQ may serve as a promising molecular target for the prevention and treatment of AD.
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spelling doaj-art-8097a13c8ec6437b8575aab9745a76852025-02-06T00:00:02ZengWileyNeural Plasticity1687-54432025-01-01202510.1155/np/3934591Overexpression of SFPQ Improves Cognition and Memory in AD MiceJinshan Tie0Hongxiang Wu1Wei Liu2Yuying Li3Lu Li4Suju Zhao5Zhijiao Yuan6Khan Mahmood7Shaochun Chen8Huidong Wu9School of RehabilitationSchool of RehabilitationSchool of RehabilitationSchool of RehabilitationSchool of RehabilitationSchool of RehabilitationSchool of RehabilitationSchool of RehabilitationSchool of RehabilitationSchool of RehabilitationAlzheimer’s disease (AD) is a complex neurodegenerative disorder with multifaceted pathogenesis, which has been extensively investigated, yet effective treatments remain lacking. Splicing factor proline and glutamine rich (SFPQ) is known to play a crucial role in neurodegenerative diseases, including antioxidant-related functions and regulating gene expression within brain neurons. However, the specific role of SFPQ in AD pathology is not well understood. In this study, an AD mouse model was established through lateral ventricular injection of amyloid-beta1–42 (Aβ1–42). Subsequently, adeno-associated virus was administered to overexpress SFPQ in the hippocampus of AD mice. The results demonstrate that SFPQ overexpression improves recognition and memory in AD mice, while reducing AD-related marker proteins such as amyloid precursor protein (APP) and Tau. Additionally, synaptic and memory-associated proteins, as well as antioxidant proteins like glutathione S-transferase (GST) and heme oxygenase-1 (HO-1), were upregulated. The ratio of antiapoptotic protein Bcl-2 to proapoptotic protein Bax also increased. Furthermore, phosphorylated phosphoinositide 3-kinase (p-PI3K)/PI3K and phosphorylated protein kinase B (p-AKT)/AKT ratios were elevated, indicating activation of the PI3K/AKT signaling pathway. These findings suggest that SFPQ may serve as a promising molecular target for the prevention and treatment of AD.http://dx.doi.org/10.1155/np/3934591
spellingShingle Jinshan Tie
Hongxiang Wu
Wei Liu
Yuying Li
Lu Li
Suju Zhao
Zhijiao Yuan
Khan Mahmood
Shaochun Chen
Huidong Wu
Overexpression of SFPQ Improves Cognition and Memory in AD Mice
Neural Plasticity
title Overexpression of SFPQ Improves Cognition and Memory in AD Mice
title_full Overexpression of SFPQ Improves Cognition and Memory in AD Mice
title_fullStr Overexpression of SFPQ Improves Cognition and Memory in AD Mice
title_full_unstemmed Overexpression of SFPQ Improves Cognition and Memory in AD Mice
title_short Overexpression of SFPQ Improves Cognition and Memory in AD Mice
title_sort overexpression of sfpq improves cognition and memory in ad mice
url http://dx.doi.org/10.1155/np/3934591
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