98%
921
2 minutes
20
The low-density lipoprotein receptor (LDLR) is a major apolipoprotein receptor that regulates cholesterol homeostasis. LDLR deficiency is associated with cognitive impairment by the induction of synaptopathy in the hippocampus. Despite the close relationship between LDLR and neurodegenerative disorders, proteomics research for protein profiling in the LDLR knockout (KO) model remains insufficient. Therefore, understanding LDLR KO-mediated differential protein expression within the hippocampus is crucial for elucidating a role of LDLR in neurodegenerative disorders. In this study, we conducted first-time proteomic profiling of hippocampus tissue from LDLR KO mice using tandem mass tag (TMT)-based MS analysis. LDLR deficiency induces changes in proteins associated with the transport of diverse molecules, and activity of kinase and catalyst within the hippocampus. Additionally, significant alterations in the expression of components in the major synaptic pathways were found. Furthermore, these synaptic effects were verified using a data-independent acquisition (DIA)-based proteomic method. Our data will serve as a valuable resource for further studies to discover the molecular function of LDLR in neurodegenerative disorders.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/pmic.202400152 | DOI Listing |
J Steroid Biochem Mol Biol
September 2025
Helix Research Lab, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, Tamil Nadu 602105, India.
7-Ketocholesterol (7-KC), a cytotoxic cholesterol oxidation product, drives oxidative stress, inflammation, and apoptosis in cardiovascular, neurodegenerative, and metabolic disorders. Current lipid-lowering agents, such as statins, do not eliminate pre-formed oxysterols, highlighting an unmet therapeutic need. Guggulsterone(GGS), a steroidal phytoconstituent from Commiphora mukul, exhibits dual-function potential by reducing 7-KC formation through antioxidant, anti-inflammatory, and Nrf2-activating effects, while enhancing cholesterol efflux via LDLR and ABC transporters.
View Article and Find Full Text PDFResearch (Wash D C)
June 2025
Department of Pharmacology, School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, Anhui, China.
Apolipoprotein E (ApoE) has been implicated in neurodegenerative diseases; however, its function and underlying mechanisms in depression remain elusive. In this study, we employed chronic social defeat stress (CSDS) to establish a mouse model of depression and observed significantly reduced ApoE expression in the hippocampus. By leveraging ApoE knockout ( ) and knockdown (ApoE-KD) mouse models, we demonstrated that ApoE deficiency induced depression-like behaviors, which were closely associated with impaired GABAergic synaptic transmission and down-regulation of ApoE receptors and K-Cl cotransporter 2 (KCC2).
View Article and Find Full Text PDFCell Mol Neurobiol
May 2025
Division of Anatomy and Neurobiology, Faculty of Medicine, Medical University of Gdansk, Dębinki 1, 80-211, Gdańsk, Poland.
Hypercholesterolemia (Hch) is a risk factor for cerebrovascular and neurodegenerative diseases, manifesting with symptoms that vary depending on damage to specific brain regions. Hch triggers inflammatory responses and cell death. However, the progression of these processes in relation to the duration of Hch and the location of pathology in the central nervous system remains unclear.
View Article and Find Full Text PDFProteomics
February 2025
Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul, South Korea.
The low-density lipoprotein receptor (LDLR) is a major apolipoprotein receptor that regulates cholesterol homeostasis. LDLR deficiency is associated with cognitive impairment by the induction of synaptopathy in the hippocampus. Despite the close relationship between LDLR and neurodegenerative disorders, proteomics research for protein profiling in the LDLR knockout (KO) model remains insufficient.
View Article and Find Full Text PDFJ Clin Invest
November 2024
Division of Molecular Medicine, Department of Medicine, and.
Clonal hematopoiesis (CH) increases inflammasome-linked atherosclerosis, but the mechanisms by which CH mutant cells transmit inflammatory signals to nonmutant cells are largely unknown. To address this question, we transplanted 1.5% Jak2V617F (Jak2VF) bone marrow (BM) cells with 98.
View Article and Find Full Text PDF