Impact Of Cholesterol Research Articles

Role of cholesterol in modulating brain hyperexcitability.

Cholesterol is a critical molecule in the central nervous system, and imbalances in the synthesis and metabolism of brain cholesterol can result in a range of pathologies, including those related to hyperexcitability. The impact of cholesterol on disorders of epilepsy and developmental and epileptic encephalopathies is an area of growing interest. Cholesterol cannot cross the blood-brain barrier, and thus the brain synthesizes and metabolizes its own pool of cholesterol. The primary metabolic enzyme for brain cholesterol is cholesterol 24-hydroxylase (CH24H), which metabolizes cholesterol into 24S-hydroxycholesterol (24HC). Dysregulation of CH24H and 24HC can affect neuronal excitability through a range of mechanisms. 24HC is a positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors and can increase glutamate release via tumor necrosis factor-α-dependent pathways. Increasing cholesterol metabolism can lead to dysfunction of excitatory amino acid transporter 2 and impair glutamate reuptake. Finally, overstimulation of NMDA receptors can further activate metabolism of cholesterol, leading to a vicious cycle of overactivation. All of these mechanisms increase extracellular glutamate and can lead to hyperexcitability. For these reasons, the cholesterol pathway represents a new potential mechanistic target for antiseizure medications. CH24H inhibition has been shown to decrease seizure behavior and improve survival in multiple animal models of epilepsy and could be a promising new mechanism of action for the treatment of neuronal hyperexcitability and developmental and epileptic encephalopathies.

Comparative analysis of cholesterol and its alternative squalene: The impact on growth and lipid metabolism in coin-sized Eriocheir sinensis

Cholesterol is crucial for the growth and development of crabs, but its high cost limits its widespread use in feed. Squalene, a key precursor in cholesterol synthesis, has the potential to replace cholesterol, but its effectiveness in promoting crab growth and cholesterol levels remains unclear. This study investigated the cholesterol and squalene requirements of coin-sized Eriocheir sinensis, the impact of cholesterol and squalene on growth and lipid metabolism, and the relative bioavailability of squalene. A total of 420 coin-sized crabs were divided into seven experimental groups and fed different diets for eight weeks. The diets included three cholesterol levels at 0 % (Control), 0.2 %, and 0.4 %, and four squalene levels at 0.05 %, 0.1 %, 0.2 %, and 0.4 %. Here, we reported that both 0.2 % and 0.4 % cholesterol significantly increased final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR) of coin-sized crabs, and 0.2 % cholesterol showed the best growth-promoting effect. Similarly, increasing dietary squalene levels significantly enhanced FBW, WGR, and SGR, with 0.4 % squalene providing the best growth-promoting effect. Additionally, 0.4 % squalene significantly decreased hepatopancreas index (HSI), but did not affect molting frequency (MF). Interestingly, although squalene and cholesterol exerted opposite effects on biochemical indices such as cholesterol and triglyceride levels in the hemolymph, both promoted cholesterol deposition in the hepatopancreas. Relative bioavailability of squalene compared to cholesterol on growth and cholesterol deposition was 82.61 % and 81.73 %, respectively, which might be closely related to lipid metabolism-related genes. In conclusion, the study revealed that similar to cholesterol, squalene was important for crab growth and cholesterol deposition, and squalene could serve as a potential substitute to reduce the reliance on cholesterol in crab feed.

Machine learning analysis of serum cholesterol's impact on knee osteoarthritis progression.

The controversy surrounding whether serum total cholesterol is a risk factor for the graded progression of knee osteoarthritis (KOA) has prompted this study to develop an authentic prediction model using a machine learning (ML) algorithm. The objective was to investigate whether serum total cholesterol plays a significant role in the progression of KOA. This cross-sectional study utilized data from the public database DRYAD. LASSO regression was employed to identify risk factors associated with the graded progression of KOA. Additionally, six ML algorithms were utilized in conjunction with clinical features and relevant variables to construct a prediction model. The significance and ranking of variables were carefully analyzed. The variables incorporated in the model include JBS3, Diabetes, Hypertension, HDL, TC, BMI, SES, and AGE. Serum total cholesterol emerged as a significant risk factor for the graded progression of KOA in all six ML algorithms used for importance ranking. XGBoost algorithm was based on the combined best performance of the training and validation sets. The ML algorithm enables predictive modeling of risk factors for the progression of the KOA K-L classification and confirms that serum total cholesterol is an important risk factor for the progression of KOA.

The Impact of Cholesterol on Stroke Outcomes: A Cross-Sectional Analysis in Central Java

Introduction: Stroke remains a leading cause of mortality and morbidity globally, with variations in subtypes and risk factors observed across populations. The role of cholesterol in stroke, particularly its association with ischemic and hemorrhagic subtypes, continues to be investigated. This study aimed to examine the relationship between cholesterol levels and stroke outcomes in a Central Javanese population. Methods: A cross-sectional study was conducted at hospitals in Central Java, Indonesia. Data were collected from medical records of patients diagnosed with ischemic or hemorrhagic stroke between January and December 2022. Demographic information, stroke subtype, and cholesterol levels were analyzed. Statistical tests were employed to assess the association between cholesterol and stroke outcomes. Results: The study included 68 patients (34 ischemic, 34 hemorrhagic). The majority of hemorrhagic stroke patients were female (52.9%), while ischemic stroke patients were predominantly male (64.7%). The mean cholesterol level for hemorrhagic stroke patients was 202.59 mg/dL, and for ischemic stroke patients, it was 190.26 mg/dL. Statistical analysis revealed no significant association between cholesterol levels and stroke subtype (p > 0.05). Conclusion: The findings suggest that cholesterol levels may not be a primary determinant of stroke subtype in this Central Javanese population. Further research is warranted to explore other potential risk factors and their interplay with cholesterol in influencing stroke outcomes.

Impact of cholesterol on the structure and phase separation of DPPC Langmuir monolayers: Experiments and simulations

Cholesterol is a lipid that plays a key role mainly in the plasma membrane of animal cells, determining their structural and mechanical properties. While Langmuir monolayers have been a traditional model for studying these membranes, they may not fully capture microscopic phenomena. We studied mixed Langmuir monolayers of DPPC and cholesterol in various proportions, using a Langmuir trough for surface compression isotherms and micro-Brewster Angle Microscopy (MicroBAM) for imaging. Furthermore, atomistic Molecular Dynamics (MD) simulations were used to examine molecular distributions, geometric conformations, and emergence of a gas phase in the monolayers. Both experimental and simulation results were compared to obtain a comprehensive understanding. The results reveal strong attraction between DPPC tails and cholesterol, increasing monolayer stiffness and density. These interactions align the lipid tails more perpendicularly to the water surface, effectively minimizing their projected area and preventing tail entanglement. Consequently, the reduced flexibility triggers a phase separation in the monolayer at smaller areas per lipid, with low-density voids and denser regions, as observed in both MicroBAM and simulations. These outcomes emphasize the critical role of cholesterol in biological membranes. Finally, the consistency of MD simulations with experiments validate them as a valuable tool for investigating lipid monolayer behavior.

Cholesterol Modulation Attenuates the AD-like Phenotype Induced by Herpes Simplex Virus Type 1 Infection.

Cholesterol, a crucial component of cell membranes, influences various biological processes, including membrane trafficking, signal transduction, and host-pathogen interactions. Disruptions in cholesterol homeostasis have been linked to congenital and acquired conditions, including neurodegenerative disorders such as Alzheimer's disease (AD). Previous research from our group has demonstrated that herpes simplex virus type I (HSV-1) induces an AD-like phenotype in several cell models of infection. This study explores the interplay between cholesterol and HSV-1-induced neurodegeneration. The impact of cholesterol was determined by modulating its levels with methyl-beta-cyclodextrin (MβCD) using the neuroblastoma cell lines SK-N-MC and N2a. We have found that HSV-1 infection triggers the intracellular accumulation of cholesterol in structures resembling endolysosomal/autophagic compartments, a process reversible upon MβCD treatment. Moreover, MβCD exhibits inhibitory effects at various stages of HSV-1 infection, underscoring the importance of cellular cholesterol levels, not only in the viral entry process but also in subsequent post-entry stages. MβCD also alleviated several features of AD-like neurodegeneration induced by viral infection, including lysosomal impairment and intracellular accumulation of amyloid-beta peptide (Aβ) and phosphorylated tau. In conclusion, these findings highlight the connection between cholesterol, neurodegeneration, and HSV-1 infection, providing valuable insights into the underlying mechanisms of AD.

Molecular Insights into the Effect of Cholesterol on the Binding of Bicarbonate Ions in Band 3 Protein.

Band 3, or anion exchanger 1 (AE1), is one of the indispensable transmembrane proteins involved in the effective respiratory process of the human body and is primarily responsible for the exchange of bicarbonate and chloride anions across the plasma membrane of erythrocyte. However, the molecular mechanism of ion transport of Band 3 is not completely understood, yet. In this work, we systematically investigate the key binding sites of bicarbonate ions in Band 3 and the impact of cholesterol (CHOL) in lipid bilayers on bicarbonate ion binding using all-atom molecular dynamics (MD) simulations. We examine the dynamics of interactions of bicarbonate ions with Band 3 in the microsecond time scale and calculate the binding free energy of the anion in Band 3. The results indicate that the residue R730 of Band 3 is the most probable binding site for bicarbonate ions. CHOL enhances the bicarbonate ion binding by influencing the conformational stability of Band 3 and compressing the volume of the Band 3 cavity. These findings provide some insights into the bicarbonate ion binding in Band 3 and are helpful for understanding the anion exchange of Band 3.

WS04.02 Impact of cholesterol on the functioning of CFTR modulators

Objectives: Orkambi is a combination of two CFTR modulators: corrector VX-809 and potentiator VX-770. Both drugs have been separately shown to bind CFTR at a protein-lipid interface, albeit at various locations on the channel. The cholesterol-rich membrane surrounding CFTR plays an important role in its proper folding. However, minimal research has been done to understand the potential role cholesterol plays in facilitating drug-CFTR interactions. Here we investigated the role cholesterol plays in Orkambi’s interaction with mammalian membrane and in folding of helical hairpin constructs consisting of transmembrane segments 3 and 4 (TM3/4) of CFTR’s transmembrane domain 1.

Dual mechanisms of cholesterol-GPCR interactions that depend on membrane phospholipid composition

Cholesterol is a critical component of mammalian cell membranes and an allosteric modulator of G protein-coupled receptors (GPCRs), but divergent views exist on the mechanisms by which cholesterol influences receptor functions. Leveraging the benefits of lipid nanodiscs, i.e., quantitative control of lipid composition, we observe distinct impacts of cholesterol in the presence and absence of anionic phospholipids on the function-related conformational dynamics of the human A2A adenosine receptor (A2AAR). Direct receptor-cholesterol interactions drive activation of agonist-bound A2AAR in membranes containing zwitterionic phospholipids. Intriguingly, the presence of anionic lipids attenuates cholesterol's impact through direct interactions with the receptor, highlighting a more complex role for cholesterol that depends on membrane phospholipid composition. Targeted amino acid replacements at two frequently predicted cholesterol interaction sites showed distinct impacts of cholesterol at different receptor locations, demonstrating the ability to delineate different roles of cholesterol in modulating receptor signaling and maintaining receptor structural integrity.

Cholesterol and Phosphoinositides in Cilia Biology.

Cilia are evolutionarily conserved organelles that can be found on virtually every cell. They appear as hair-like structures emanating from the cellular surface either as single or as bundles of cilia. There, they sense external stimuli and translate them into intracellular signals. Motile cilia beat for the generation of locomotion of unicellular organisms or fluid flow in certain body cavities of vertebrate organisms. Defects in cilia are detrimental and account for the development of ciliopathies, one of the fastest-growing family of afflictions. In the past decade, membrane lipids, such as cholesterol and phosphoinositides, have emerged as essential elements in both the signal transduction via cilia and the building of cilia itself. Here, we summarize the current knowledge on the impact of cholesterol and phosphoinositides on cilium biology.

Impact of cholesterol and Lumacaftor on the folding of CFTR helical hairpins

Cystic fibrosis (CF) is caused by mutations in the gene that codes for the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR). Recent advances in CF treatment have included use of small-molecule drugs known as modulators, such as Lumacaftor (VX-809), but their detailed mechanism of action and interplay with the surrounding lipid membranes, including cholesterol, remain largely unknown. To examine these phenomena and guide future modulator development, we prepared a set of wild type (WT) and mutant helical hairpin constructs consisting of CFTR transmembrane (TM) segments 3 and 4 and the intervening extracellular loop (termed TM3/4 hairpins) that represent minimal membrane protein tertiary folding units. These hairpin variants, including CF-phenotypic loop mutants E217G and Q220R, and membrane-buried mutant V232D, were reconstituted into large unilamellar phosphatidylcholine (POPC) vesicles, and into corresponding vesicles containing 70 mol% POPC +30 mol% cholesterol, and studied by single-molecule FRET and circular dichroism experiments. We found that the presence of 30 mol% cholesterol induced an increase in helicity of all TM3/4 hairpins, suggesting an increase in bilayer cross-section and hence an increase in the depth of membrane insertion compared to pure POPC vesicles. Importantly, when we added the corrector VX-809, regardless of the presence or absence of cholesterol, all mutants displayed folding and helicity largely indistinguishable from the WT hairpin. Fluorescence spectroscopy measurements suggest that the corrector alters lipid packing and water accessibility. We propose a model whereby VX-809 shields the protein from the lipid environment in a mutant-independent manner such that the WT scaffold prevails. Such ‘normalization’ to WT conformation is consistent with the action of VX-809 as a protein-folding chaperone.

Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH.

Excessive dietary cholesterol is preferentially stored in the liver, favoring the development of nonalcoholic steatohepatitis (NASH), characterized by progressive hepatic inflammation and fibrosis. Emerging evidence indicates a critical contribution of hepatic macrophages to NASH severity. However, the impact of cholesterol on these cells in the setting of NASH remains elusive. Here, we demonstrate that the dietary cholesterol content directly affects hepatic macrophage global gene expression. Our findings suggest that the modifications triggered by prolonged high cholesterol intake induce long-lasting hepatic damage and support the expansion of a dysfunctional pro-fibrotic restorative macrophage population even after cholesterol reduction. The present work expands the understanding of the modulatory effects of cholesterol on innate immune cell transcriptome and may help identify novel therapeutic targets for NASH intervention.

Green formulation, characterization, antifungal and biological safety evaluation of terbinafine HCl niosomes and niosomal gels manufactured by eco-friendly green method

Terbinafine (TER) is a promising candidate medication for the topical treatment of fungal infections. However, its solubility in water and skin permeability are limited. To overcome these limitations, a Terbinafine niosome and niosomal gel was developed. The impact of cholesterol:surfactants on terbinafine incorporated niosome (terbinasome) preparations was examined. Differential scanning calorimetry (DSC), photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to assess the morphological features of terbinasome and the physicochemical characteristics of TER in terbinasome. The obtained results has shown that Chol enhanced the diameter of the terbinasome from 123.20 ± 2.86 to 701.93 ± 17.72 nm. The highest encapsulation of terbinafine was estimated to be around 66% due to the cholesterol:surfactants ratio in the terbinasome was 1:3 and 1:6. Additional examination has revealed that changes in the cholesterol:surfactants ratio can result in a change in the PDI value of between 0.421 ± 0.004 and 0.712 ± 0.011. The terbinasome gel was prepared and tested for pharmaceutical testing, including pH, viscosity, spreadability, and stability. The percentage of TER dissolution from terbinasome were determined more than 80% and showed quickest drug release. In a cutaneous permeability examination, the quantity of TER in the cutaneous layers and the receiver compartment were higher for the terbinasome gel than for the TER simple gel. The terbinasome's cell viability was around 90% (HFF cell line) and MTT experiment demonstrated that the terbinasome was not cytotoxic. The MIC of the terbinasome was lower than pure drug against Aspergillus, Fusarium, and Trichophyton. The terbinasomal gels were non-irritant (score < 2) in the cutaneous irritation examination performed on Wistar rats. The research suggests that the optimized terbinasome may be used as a nano-vesicle for TER drug administration, hence opening up new possibilities for the treatment of cutaneous infections.

Insight into the Impact of Oxidative Stress on the Barrier Properties of Lipid Bilayer Models.

As a new field of oxidative stress-based therapy, cold physical plasma is a promising tool for several biomedical applications due to its potential to create a broad diversity of reactive oxygen and nitrogen species (RONS). Although proposed, the impact of plasma-derived RONS on the cell membrane lipids and properties is not fully understood. For this purpose, the changes in the lipid bilayer functionality under oxidative stress generated by an argon plasma jet (kINPen) were investigated by electrochemical techniques. In addition, liquid chromatography-tandem mass spectrometry was employed to analyze the plasma-induced modifications on the model lipids. Various asymmetric bilayers mimicking the structure and properties of the erythrocyte cell membrane were transferred onto a gold electrode surface by Langmuir-Blodgett/Langmuir-Schaefer deposition techniques. A strong impact of cholesterol on membrane permeabilization by plasma-derived species was revealed. Moreover, the maintenance of the barrier properties is influenced by the chemical composition of the head group. Mainly the head group size and its hydrogen bonding capacities are relevant, and phosphatidylcholines are significantly more susceptible than phosphatidylserines and other lipid classes, underlining the high relevance of this lipid class in membrane dynamics and cell physiology.

Impact of cholesterol and sphingomyelin on intrinsic membrane permeability

Transwell experiments with Caco-2 or MDCK cells are the gold standard for determining the intestinal permeability of chemicals. The intrinsic membrane permeability (P0), that can be extracted from these experiments, might be comparable to P0 measured in black lipid membrane (BLM) experiments and P0 predicted by the solubility-diffusion model. Unfortunately, the overlap between experimental P0,Caco-2/MDCK and P0,BLM data is very small. So far, differences between both approaches have been attributed to the cholesterol and sphingomyelin content of cell membranes, but the database is too sparse to thoroughly test this theory. To create a diverse dataset, we measured P0,BLM of ten chemicals in BLM experiments using DPhPC and DPhPC/cholesterol/sphingomyelin membranes. The results were compared to predicted BLM data and experimental Caco-2/MDCK data obtained from literature. While P0,BLM of all chemicals was well predicted by the solubility-diffusion model, P0,Caco-2/MDCK was only predictable for rather hydrophilic compounds with logarithmic hexadecane/water partition coefficients below −0.5. The effect of cholesterol and sphingomyelin on P0,BLM was negligibly small.

Impact of cholesterol on proinflammatory monocyte production by the bone marrow.

AimPreclinical work indicates that low-density lipoprotein cholesterol (LDL-C) not only drives atherosclerosis by directing the innate immune response at plaque level but also augments proinflammatory monocyte production in the bone marrow (BM) compartment. In this study, we aim to unravel the impact of LDL-C on monocyte production in the BM compartment in human subjects.Methods and resultsA multivariable linear regression analysis in 12 304 individuals of the EPIC-Norfolk prospective population study showed that LDL-C is associated with monocyte percentage (β = 0.131 [95% CI: 0.036–0.225]; P = 0.007), at the expense of granulocytes (β = −0.876 [95% CI: −1.046 to −0.705]; P < 0.001). Next, we investigated whether altered haematopoiesis could explain this monocytic skewing by characterizing CD34+ BM haematopoietic stem and progenitor cells (HSPCs) of patients with familial hypercholesterolaemia (FH) and healthy normocholesterolaemic controls. The HSPC transcriptomic profile of untreated FH patients showed increased gene expression in pathways involved in HSPC migration and, in agreement with our epidemiological findings, myelomonocytic skewing. Twelve weeks of cholesterol-lowering treatment reverted the myelomonocytic skewing, but transcriptomic enrichment of monocyte-associated inflammatory and migratory pathways persisted in HSPCs post-treatment. Lastly, we link hypercholesterolaemia to perturbed lipid homeostasis in HSPCs, characterized by lipid droplet formation and transcriptomic changes compatible with increased intracellular cholesterol availability.ConclusionsCollectively, these data highlight that LDL-C impacts haematopoiesis, promoting both the number and the proinflammatory activation of circulating monocytes. Furthermore, this study reveals a potential contributory role of HSPC transcriptomic reprogramming to residual inflammatory risk in FH patients despite cholesterol-lowering therapy.

Effects of cholesterol on chlorzoxazone translocation across POPC bilayer.

Cholesterol plays a crucial role in modulating the physicochemical properties of membranes, thus influencing the membrane transport of drugs. In this paper, the effects caused by cholesterol on the membrane transport of chlorzoxazone (CZX), a centrally acting muscle relaxant drug, were probed through molecular dynamics simulations. POPC was selected as the model lipid, and three different cholesterol concentrations (0%, 20%, and 50% CHOL) were considered. The outcomes reveal that the area per lipid of POPC decreases and the order parameter increases with enhanced concentration of CHOL. CZX prefers to localize at the interface between the headgroup region and the hydrophobic tail region of POPC, and the main energy barrier occurs in the hydrophobic region. The impact of CHOL on the free energy profile is correlated with concentration: low concentration facilitates CZX permeation, while high concentration hinders CZX permeation. Our findings coincide with experimental results, enhancing the mechanism understanding of how drug molecules are transported through membranes in the presence of CHOL. • The effects caused by cholesterol (CHOL) on the membrane transport of chlorzoxazone (CZX) were studied. • Low CHOL concentration facilitates CZX permeation, while high concentration hinders CZX permeation. • Our findings improve the mechanism understanding of CHOL effects on CZX translocation across membrane.

Direct Regulation of the T Cell Antigen Receptor's Activity by Cholesterol.

Biological membranes consist of hundreds of different lipids that together with the embedded transmembrane (TM) proteins organize themselves into small nanodomains. In addition to this function of lipids, TM regions of proteins bind to lipids in a very specific manner, but the function of these TM region-lipid interactions is mostly unknown. In this review, we focus on the role of plasma membrane cholesterol, which directly binds to the αβ T cell antigen receptor (TCR), and has at least two opposing functions in αβ TCR activation. On the one hand, cholesterol binding to the TM domain of the TCRβ subunit keeps the TCR in an inactive, non-signaling conformation by stabilizing this conformation. This assures that the αβ T cell remains quiescent in the absence of antigenic peptide-MHC (the TCR's ligand) and decreases the sensitivity of the T cell toward stimulation. On the other hand, cholesterol binding to TCRβ leads to an increased formation of TCR nanoclusters, increasing the avidity of the TCRs toward the antigen, thus increasing the sensitivity of the αβ T cell. In mouse models, pharmacological increase of the cholesterol concentration in T cells caused an increase in TCR clustering, and thereby enhanced anti-tumor responses. In contrast, the γδ TCR does not bind to cholesterol and might be regulated in a different manner. The goal of this review is to put these seemingly controversial findings on the impact of cholesterol on the αβ TCR into perspective.

Mimicking the Mammalian Plasma Membrane: An Overview of Lipid Membrane Models for Biophysical Studies.

Cell membranes are very complex biological systems including a large variety of lipids and proteins. Therefore, they are difficult to extract and directly investigate with biophysical methods. For many decades, the characterization of simpler biomimetic lipid membranes, which contain only a few lipid species, provided important physico-chemical information on the most abundant lipid species in cell membranes. These studies described physical and chemical properties that are most likely similar to those of real cell membranes. Indeed, biomimetic lipid membranes can be easily prepared in the lab and are compatible with multiple biophysical techniques. Lipid phase transitions, the bilayer structure, the impact of cholesterol on the structure and dynamics of lipid bilayers, and the selective recognition of target lipids by proteins, peptides, and drugs are all examples of the detailed information about cell membranes obtained by the investigation of biomimetic lipid membranes. This review focuses specifically on the advances that were achieved during the last decade in the field of biomimetic lipid membranes mimicking the mammalian plasma membrane. In particular, we provide a description of the most common types of lipid membrane models used for biophysical characterization, i.e., lipid membranes in solution and on surfaces, as well as recent examples of their applications for the investigation of protein-lipid and drug-lipid interactions. Altogether, promising directions for future developments of biomimetic lipid membranes are the further implementation of natural lipid mixtures for the development of more biologically relevant lipid membranes, as well as the development of sample preparation protocols that enable the incorporation of membrane proteins in the biomimetic lipid membranes.

Impact of Cholesterol on the Stability of Monomeric and Dimeric Forms of the Translocator Protein TSPO: A Molecular Simulation Study.

The translocator protein (TSPO) is a transmembrane protein present across the three domains of life. Its functional quaternary structure consists of one or more subunits. In mice, the dimer-to-monomer equilibrium is shifted in vitro towards the monomer by adding cholesterol, a natural component of mammalian membranes. Here, we present a coarse-grained molecular dynamics study on the mouse protein in the presence of a physiological content and of an excess of cholesterol. The latter turns out to weaken the interfaces of the dimer by clusterizing mostly at the inter-monomeric space and pushing the contact residues apart. It also increases the compactness and the rigidity of the monomer. These two factors might play a role for the experimentally observed incremented stability of the monomeric form with increased content of cholesterol. Comparison with simulations on bacterial proteins suggests that the effect of cholesterol is much less pronounced for the latter than for the mouse protein.