AI Article Synopsis

  • Alzheimer’s disease (AD) is characterized by the aggregation of amyloid-β (Aβ) peptides into toxic structures, but human serum albumin can inhibit this process by binding to Aβ and preventing its fibrous formation.
  • A phase II clinical trial demonstrated that albumin-plasma exchange can reduce cognitive decline in AD patients, suggesting albumin's potential protective role.
  • The presence of other hydrophobic molecules like cholesterol and fatty acids can interfere with albumin’s ability to inhibit Aβ fibrillization, linking dietary factors to AD risk.

Article Abstract

Central to Alzheimer's disease (AD) pathology is the assembly of monomeric amyloid-β peptide (Aβ) into oligomers and fibers. The most abundant protein in the blood plasma and cerebrospinal fluid is human serum albumin. Albumin can bind to Aβ and is capable of inhibiting the fibrillization of Aβ at physiological (μM) concentrations. The ability of albumin to bind Aβ has recently been exploited in a phase II clinical trial, which showed a reduction in cognitive decline in AD patients undergoing albumin-plasma exchange. Here we explore the equilibrium between Aβ monomer, oligomer and fiber in the presence of albumin. Using transmission electron microscopy and thioflavin-T fluorescent dye, we have shown that albumin traps Aβ as oligomers, 9 nm in diameter. We show that albumin-trapped Aβ oligomeric assemblies are not capable of forming ion channels, which suggests a mechanism by which albumin is protective in Aβ-exposed neuronal cells. In vivo albumin binds a variety of endogenous and therapeutic exogenous hydrophobic molecules, including cholesterol, fatty acids and warfarin. We show that these molecules bind to albumin and suppress its ability to inhibit Aβ fiber formation. The interplay between Aβ, albumin and endogenous hydrophobic molecules impacts Aβ assembly; thus, changes in cholesterol and fatty acid levels in vivo may impact Aβ fibrillization, by altering the capacity of albumin to bind Aβ. These observations are particularly intriguing given that high cholesterol or fatty acid diets are well-established risk factors for late-onset AD.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2018.01.008DOI Listing

Publication Analysis

Top Keywords

cholesterol fatty
16
12
albumin bind
12
bind aβ
12
albumin
10
fiber formation
8
fatty acids
8
acids warfarin
8
aβ oligomers
8
hydrophobic molecules
8

Similar Publications

Oleic acid liposomes (OALs) are novel vesicular carriers ofunsaturated fatty acids and their corresponding ionized species, arranged within an enclosed lipid bilayer. This study aimed to encapsulate moxifloxacin HCl (MOX), a broad-spectrum antibacterial drug into OALs for effective treatment of Methicillin-resistant Staphylococcus aureus (MRSA) infection through topical application. Various OALs were formulatedby combining varied quantities of phosphatidylcholine (PC), oleic acid (OA), and cholesterol (CH) with 50 mg of MOX.

View Article and Find Full Text PDF

Exhaled breath offers an interesting matrix of low invasive sampling of potentially relevant information about the organism's metabolism in the form of volatile organic compounds (VOC). The VOC can be exhaled by the ructus (Islam et al., 2023) or passed the blood-lung barrier for expiration through the lungs.

View Article and Find Full Text PDF

Lipid-laden uterus: Investigating uterine fibroids and lipid association.

Pathol Res Pract

December 2024

Nitte (Deemed To Be University), KS Hegde Medical Academy (KSHEMA), Department of obstetrics and gynecology, India; Nitte (Deemed To Be University), KS Hegde Medical Academy (KSHEMA), KSHEMA IVF Fertility & Reproductive Medicine Centre India, India.

Uterine Fibroids (UF) are the most common (about 70 % cases) benign gynecological smooth muscle tumors of the uterus in women of reproductive age, characterized by abnormal cholesterol, lipoproteins, and triglyceride levels, and are a major public health concern. Despite its high prevalence, this condition remains complex and poorly understood. These tumors are hormone-dependent and hormones and lipid levels are inversely related.

View Article and Find Full Text PDF

Metabolic syndrome (MetS) is driven by a complex interplay of genetic, lifestyle, and dietary factors, leading to weight gain, insulin resistance, dyslipidemia, and chronic inflammation. Gut microbiota dysbiosis has been recently recognized as a key contributor to MetS, leading to advancements in gut microbiome-based interventions to improve health outcomes. Considering the unique challenges associated with the use of pre/probiotics, short-chain fatty acids (SCFA), also known as postbiotics, have emerged as promising therapeutic agents due to their role in modulating host metabolism and physiology.

View Article and Find Full Text PDF

Decorin alleviates non-alcoholic fatty liver disease in rats with polycystic ovary syndrome.

Tissue Cell

December 2024

Medical Physiology Department, Faculty of Medicine, Zagazig University, P.O. Box 44519, Zagazig, Egypt. Electronic address:

Endocrine multisystem defect polycystic ovary syndrome (PCOS) causes hyperandrogenism and infertility. Half of PCOS women have (non-alcoholic fatty liver disease) NAFLD, which increases metabolic disease risk. We tested decorin's effect on NAFLD and related processes in PCOS.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!