Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

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.202400152DOI Listing

Publication Analysis

Top Keywords

ldlr neurodegenerative
12
neurodegenerative disorders
12
ldlr
10
profiling hippocampus
8
ldlr knockout
8
ldlr deficiency
8
hippocampus
5
in-depth proteome
4
proteome profiling
4
hippocampus ldlr
4

Similar Publications

Guggulsterone as a dual-function steroidal scaffold: Cholesterol modulation and bioenhancement potential against 7-Ketocholesterol-Linked pathologies.

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 PDF

Targeting ApoE-KCC2 Signaling Rescues GABAergic Synaptic Dysfunction and Depression-like Behaviors in Mice.

Research (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 PDF

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 PDF

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 PDF

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