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| http://dx.doi.org/10.1186/s13054-021-03722-2 | DOI Listing |
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Background: The increased incidence of Alzheimer's disease (AD) rate represent an unmet medical need and thus critical for the development of novel molecular therapeutics. Recent work focusing on patients with apoE4 alleles has highlighted the association of brain cholesterol dysregulation with elevated pathological burden and neurodegeneration. These studies have highlighted the importance of the nuclear receptor Liver X receptor (LXR) for developing AD therapies.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is characterized by hallmark amyloid plaques and neurofibrillary tangles as well as by a significant loss of myelin in the cerebral cortex and other brain regions, which contributes to neurodegeneration and cognitive decline. Remyelination, of the myelin sheath by oligodendrocytes, is a process that may be impaired in neurodegenerative diseases. Depending on the severity of the disease, there occurs loss or partial damage of the myelin sheath surrounding the neuron leading to memory deficits.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Keck School of Medicine at University of Southern California, Los Angeles, CA, USA.
Background: ABCA1-mediated cholesterol transport is a central feature in many lipid- dependent diseases including APOE4-associated Alzheimer's disease and atherosclerosis-CVD. ABCA1 upregulation of RNA transcription by nuclear factors (LXR, RXR) have been associated with liver side-effects because of the common promotor element for ABCA1 and Fatty Acid Synthase. The ABCA1 agonist CS6253, derived from the C-terminal of apoE was designed to stabilize and enhance ABCA1 function, thereby providing a safe alternative to transcriptional upregulation.
View Article and Find Full Text PDFPseudo-Phosphorylated Tau Forms Paired Helical Filaments in the Presence of High-Curvature Cholesterol-Containing Lipid Membranes.
J Am Chem Soc
January 2025
Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, Massachusetts 02139, United States.
The tau protein misfolds in neurodegenerative diseases such as Alzheimer's disease (AD). These pathological tau aggregates are associated with neuronal membranes, but molecular structural information about how disease-like tau fibrils interact with the lipid membrane is scarce. Here, we use solid-state NMR to investigate the structure of a tau construct bearing four AD-relevant phospho-mimetic mutations (4E tau) with cholesterol-containing high-curvature lipid membranes, which mimic the membrane of synaptic vesicles in neurons.
View Article and Find Full Text PDFLipoprotein(a) and Atrial Fibrillation: Mechanistic Insights and Therapeutic Approaches.
Int J Med Sci
January 2025
Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, People's Republic of China.
Elevated lipoprotein(a) [Lp(a)] levels are increasingly recognized as a significant risk factor for cardiovascular diseases and may also contribute to atrial fibrillation (AF). This review investigated the indirect mechanisms through which Lp(a) may influence AF, including proatherogenic, prothrombotic, and proinflammatory pathways. Traditional lipid-lowering therapies, such as lifestyle modifications and statins, have limited effects on Lp(a) levels.
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