Background: Activating the ubiquitin-proteasome system to dismantle disease- related proteins such as tau, β-amyloid, APP, and α-synuclein is an important focus in the research of neurodegenerative proteinopathy. By analyzing the serum RNA extracted from wild-type and Alzheimer's disease (AD) transgenic mice at different ages (4, 8, and 12 months), this study revealed a new protective role of FBXL16 in AD, primarily through facilitating the degradation of disease-related proteins via the ubiquitin proteasome system.
Methods: Proteomic analysis were conducted using protein lysates from HEK293 cells overexpressing FBXL16 to identify potential interacting proteins that interact with FBXL16. Subsequent experiments demonstrated that FBXL16 promotes the proteasomal degradation of the APP protein, as evidenced by co-immunoprecipitation with MG132 and cycloheximide (CHX), immunohistochemistry (IHC) and immunocytochemistry (ICC). Memory and cognitive improvements were observed in 3×Tg AD mice through the use of a lentivirus-mediated approach to generate a brain-specific AD mouse model overexpressing FBXL16 via stereotaxic injection. Furthermore, a brain-specific conditional knockout (cko) FBXL16 mouse model was generated and employed to further confirm the functional role of FBXL 16 in AD via various behavioral tests including Morris water maze and Y-maze.
Results: The level of FBXL16 in the brains of transgenic APP/PSEN mice with AD decreased with age. Accelerated degradation of APP was observed when FBXL16 was overexpressed in the hippocampi of these AD mice via a lentivirus. This process led to notable improvements in cognitive impairments and reductions in neuroinflammation. Further studies using proteomics and bioinformatics techniques identified transcription factors and binding proteins associated with FBXL16, providing deeper insights into the potential role of FBXL16 in the regulation of AD. Finally, the in vivo effects of FBXL16 deficiency were further substantiated in cko mice, which overexpress Aβ but specifically lack FBXL16 in the brain region.
Conclusions: These findings suggest that FBXL16 could be a new regulator of AD. These findings provide a foundation for further research into drug development and potential therapeutic strategies to combat other related neurodegenerative proteinopathies.
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http://dx.doi.org/10.1186/s40364-024-00691-w | DOI Listing |
Oncol Lett
February 2025
Department of Traditional Chinese Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu 213017, P.R. China.
Pharmacol Res
December 2024
Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Institute of Clinical Pharmacy, Central South University, Changsha, Hunan 410011, China. Electronic address:
The maintenance of cardiac homeostasis necessitates proper protein turnover, which is regulated by the ubiquitin-proteasome system. F-box proteins are one type of E3 ubiquitin ligases, and accumulating evidence suggests that dysregulation of FBPs exacerbates heart diseases. Therefore, in this review, we summarized the F-box proteins present in the heart, which can be divided into three types based on their repeated sequences, namely FBXO (Fbxo32, Fbxo25, Fbxo44, Fbxo27 and Fbxo28), FBXW (Fbxw7 and Fbxw5), and FBXL (Fbxl1, Fbxl10, Fbxl16 and Fbxl2).
View Article and Find Full Text PDFBiomark Res
November 2024
Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau S.A.R, Avenida Wai Long, Macau, 999078, China.
Background: Activating the ubiquitin-proteasome system to dismantle disease- related proteins such as tau, β-amyloid, APP, and α-synuclein is an important focus in the research of neurodegenerative proteinopathy. By analyzing the serum RNA extracted from wild-type and Alzheimer's disease (AD) transgenic mice at different ages (4, 8, and 12 months), this study revealed a new protective role of FBXL16 in AD, primarily through facilitating the degradation of disease-related proteins via the ubiquitin proteasome system.
Methods: Proteomic analysis were conducted using protein lysates from HEK293 cells overexpressing FBXL16 to identify potential interacting proteins that interact with FBXL16.
Respir Res
October 2024
Department of Respiratory and Critical Care, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, 324000, China.
Chronic obstructive pulmonary disease (COPD) is an irreversible and progressive chronic inflammatory lung disease which affects millions of people worldwide. Activated fibroblasts are observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition. In this study, we identified that miR-1307-5p expression was significantly increased in lung fibroblasts derived from COPD patients.
View Article and Find Full Text PDFSci Rep
August 2024
Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan.
Chikungunya virus (CHIKV) is a single-stranded RNA virus belonging to the genus Alphavirus and is responsible for causing Chikungunya fever, a type of arboviral fever. Despite extensive research, the pathogenic mechanism of CHIKV within host cells remains unclear. In this study, an in-silico approach was used to predict that CHIKV produces micro-RNAs that target host-specific genes associated with host cellular regulatory pathways.
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