Chemistry and Physics of Lipids最新文献

{"title":"Solid lipid nanoparticles in the diagnosis and treatment of prostate cancer: A comprehensive review of two decades of advancements","authors":"Pooja Tiwary ,&nbsp;Krishil Oswal ,&nbsp;Ryan Varghese ,&nbsp;Harsh Anchan ,&nbsp;Pardeep Gupta","doi":"10.1016/j.chemphyslip.2025.105510","DOIUrl":"10.1016/j.chemphyslip.2025.105510","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PC) is one of the most prevalent malignancies among men, with a staggering 1.5 million new cases and 350,000 deaths reported globally in 2022. Conventional treatment methods, including chemotherapy, radiation therapy, surgery, and hormonal therapy, often encounter significant challenges such as systemic toxicity and diminished efficacy, particularly in the advanced stages of the disease. Treatment of prostate cancer remains a formidable challenge because of the poor water solubility of many chemotherapeutic agents, which severely limits their bioavailability. However, the rise of targeted therapies has catalyzed the development of innovative drug delivery systems designed to enhance the bioavailability and precision of therapeutic agents. Solid lipid nanoparticles (SLNs) are a promising solution that can effectively encapsulate chemotherapeutic agents and genetic materials. Their unique attributes, such as biocompatibility, controlled release profile, and customizable surface properties, make them advantageous alternatives to conventional treatment strategies, effectively addressing the inherent limitations of prostate cancer therapy.</div></div><div><h3>Methods</h3><div>To provide the context, relevant publications were searched on Google Scholar, PubMed, Science Direct, Dimension AI, and EBSCO Host using specific keywords such as controlled drug release, cationic surfactants, drug delivery, drug loading, drug encapsulation lipid, prostate cancer, surface modification, solid lipid nanoparticles (SLNs), tumor microenvironment, to list a few. We did not add any limits to the publication date during the inclusion of papers. However, it is noteworthy that the initial reports including the aforementioned keywords have been published starting from 2010.</div></div><div><h3>Conclusion</h3><div>SLNs demonstrate substantial potential as effective nanocarriers for precise delivery of chemotherapeutic agents and genetic materials to prostate cancer cells. Their targeted delivery to these cells by surface modification with suitable ligands, antigens, peptides, and other recognition molecules has enhanced therapeutic efficacy. Further research on the interaction of SLN with the tumor environment is imperative to fully comprehend the uptake pathways. Extensive translation and preclinical studies are required to determine the safety and efficacy of SLNs before their use in clinical settings.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"270 ","pages":"Article 105510"},"PeriodicalIF":3.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detergent-resistant membranes in HeLa cells. A comparative study with an electrochemical and lipidomic perspective","authors":"Anastasie Mateckaja ,&nbsp;Martina Zatloukalová ,&nbsp;Gabriel Gonzalez ,&nbsp;Richard Masař ,&nbsp;Lukáš Najdekr ,&nbsp;Zdeněk Dostál ,&nbsp;Vlastimil Dorčák ,&nbsp;Jan Vacek","doi":"10.1016/j.chemphyslip.2025.105509","DOIUrl":"10.1016/j.chemphyslip.2025.105509","url":null,"abstract":"<div><div>Two procedures are compared for the isolation of detergent-resistant membranes (DRMs) from the HeLa model cell line. The isolation was based on application of Triton X-100 followed by 4 or 18 h ultracentrifugation in sucrose (5–42.5, % <em>w</em>) or Optiprep™ (10–25, % <em>w</em>) gradients. In the fractions obtained, the total amount of protein, cholesterol, and free thiols was evaluated using spectrophotometry. Increased protein as well as free thiol contents were demonstrated in higher density fractions. In contrast, the highest cholesterol levels were observed in light or medium heavy fractions with a low proportion of sucrose or Optiprep, especially after 18 h of centrifugation. For the sucrose gradient, we used voltammetric determination of the catalytic hydrogen evolution reaction at the Hg-electrode for individual fractions. The catalytic response, expressed as the height of the presodium wave, increased from light to heavy fractions corresponding to the protein content and/or other catalytically active species. The size of the DRMs or their associates ranged from 20 to 1000 nm, independently of the isolation protocol used. Proteins typically associated with DRMs such as caveolin and flotillin and characteristic for light and medium heavy gradient fractions, were determined using immunochemistry. We studied the subcellular localization of caveolin, flotillin, raftlin and transferrin, a control protein found intracellularly in the cytoplasm. Using confocal fluorescence microscopy, we confirmed the presence of caveolin and flotillin in the cytoplasmic membrane of HeLa cells. Raftlin was identified in both the membrane, and as part of the cell nucleus. We also performed untargeted lipidomic LC-MS analysis of the individual fractions of sucrose ultracentrifugation gradient obtained after 18 h. The predominant lipid subclasses were phosphatidylcholines and diacylglycerols. Apart from cholesterol and its ester, the rest of identified lipid classes was similar to that found in full HeLa cell lysates. The presented findings could be important for interpreting interlaboratory results and may be used as a guide for further studies on DRMs.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"270 ","pages":"Article 105509"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of α-tocopherol (vitamin E) on the phase behaviour of fully-hydrated dioleoyl phosphatidylcholine membranes","authors":"Chi Long Chan ,&nbsp;Divya Malia ,&nbsp;Miguel Paez-Perez ,&nbsp;Laurent Sagalowicz ,&nbsp;Olivier Schafer ,&nbsp;Robert V. Law ,&nbsp;Nicholas J. Brooks ,&nbsp;John M. Seddon","doi":"10.1016/j.chemphyslip.2025.105507","DOIUrl":"10.1016/j.chemphyslip.2025.105507","url":null,"abstract":"<div><div>We report on the lyotropic phase behaviour of fully-hydrated mixtures of α-tocopherol (α-toc) with the unsaturated phospholipid dioleoyl phosphatidylcholine (DOPC), as studied by synchrotron small-angle x-ray diffraction. Increasing amounts of α-toc progressively swell the layer spacing of the fluid lamellar L_α phase of DOPC, and then induce a transition to an inverse hexagonal H_II phase. Low-resolution electron density profiles show that this increase is largely due to an increased thickness of the bilayer, with little change in the water layer thickness. In the range 30 – 50 mol% α-toc, additional weak low-angle peaks were observed, whose characteristic ratios are in agreement with the presence of swollen inverse bicontinuous cubic phases of spacegroups Im3m / Pn3m. This research has applications both in the biological field and for industrial product development. We show that the effect of α-toc addition in DOPC membranes has some similarities to that of cholesterol by stabilizing inverse curvature structures, which play crucial roles in cell division, membrane trafficking and endocytosis. Concerning industrial applications, the stabilization of inverted hexagonal (H_II) and swollen bicontinuous cubic phases offers the opportunity to develop new delivery systems.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"270 ","pages":"Article 105507"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoscale dynamics in model phospholipid biomembranes probed by muon spin resonance spectroscopy: The effects of membrane composition and temperature on acyl chain and cholesterol motion","authors":"Iain McKenzie ,&nbsp;Mitchell DiPasquale ,&nbsp;Maksymilian Dziura ,&nbsp;Thomas Gutberlet ,&nbsp;Nathan A. Hartwig ,&nbsp;Victoria L. Karner ,&nbsp;Robert Scheuermann ,&nbsp;Drew Marquardt","doi":"10.1016/j.chemphyslip.2025.105496","DOIUrl":"10.1016/j.chemphyslip.2025.105496","url":null,"abstract":"<div><div>The physical properties of lipid bilayers are known to depend on their composition, but there has recently been controversy about whether cholesterol (chol) does or does not stiffen biomembranes containing unsaturated phospholipids. Herein, avoided level crossing muon spin resonance (ALC-<span><math><mi>μ</mi></math></span>SR) spectroscopy has been used to probe the local dynamics in model biomembranes composed of the saturated phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), the unsaturated phospholipids 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and the sterol chol. The presence of chol significantly stiffens the acyl chains in lipid mixtures as evident from the reduction of the amplitude of restricted reorientational motion in the acyl chain at the C<span><math><msub><mrow></mrow><mrow><mn>9</mn></mrow></msub></math></span>-C₁₀ position and the increase of the torsional barrier for rotation about the bonds in the acyl chain. Swapping POPC for DOPC slightly increases the amplitude of restricted reorientational motion and decreases the torsional barrier of the acyl chains, but the magnitude of the effect is much smaller than the inclusion of chol.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"270 ","pages":"Article 105496"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different propensity to oxidation and responses to compression of unsaturated mono- and di-galactosyldiacylglycerol Langmuir monolayers: Possible role of polymorphic transitions in lipid phase in the context of energy-converting membranes","authors":"S. Benamara ,&nbsp;I. Sbartai ,&nbsp;H. Sbartai ,&nbsp;F. Moroté ,&nbsp;T. Cohen-Bouhacina ,&nbsp;C. Grauby-Heywang","doi":"10.1016/j.chemphyslip.2025.105506","DOIUrl":"10.1016/j.chemphyslip.2025.105506","url":null,"abstract":"<div><div>Monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) are the main lipids present in thylakoids, site of photosynthesis in chloroplasts. In this work we are interested in the behavior of highly unsaturated MGDG and DGDG, studied by surface pressure measurements. Compression isotherms of these lipids show that they are able to form Langmuir monolayers, remaining in liquid expanded phase during all the compression. However, measurements at constant surface pressure and compression modulus suggest that these monolayers are not stable, even if increasing the number of spread molecules seems to increase the stability, with a particularly noticeable effect in the case of MGDG as compared to DGDG. Monolayers are then transferred on mica supports and resulting Langmuir-Blodgett films are imaged by Atomic Force Microscopy. Images and height profiles reveal the presence of thicker areas showing that some molecules are ejected outside the monolayer’s plane, with a higher propensity in the case of MGDG monolayers. We discuss these results taking into account two mechanisms, which may occur jointly: the oxidation of lipid hydrophobic chains and the desorption of lipids from the interface. The desorption amplitude would be higher in the case of MGDG, due to its propensity to organize in non-bilayer nature.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"270 ","pages":"Article 105506"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic and lipidomic alterations in lung cells induced by organophosphate flame retardants","authors":"Maryam Pyambri ,&nbsp;Athina Pavlidou ,&nbsp;Sílvia Lacorte ,&nbsp;Joaquim Jaumot ,&nbsp;Carmen Bedia","doi":"10.1016/j.chemphyslip.2025.105508","DOIUrl":"10.1016/j.chemphyslip.2025.105508","url":null,"abstract":"<div><div>Organophosphate flame retardants (OPFRs) are widely used as additives in plastics, electronics, and construction materials due to their flame-retardant properties. However, previous evidence suggests that OPFRs may pose potential respiratory health risks, including airway hyperresponsiveness, impaired lung function, and potential carcinogenic effects. This study evaluated the effects of seven OPFRs—TBOEP, TPhP, EHDPhP, TDCPP, TEHP, TCP, and TCEP—on the phenotype and lipidomic profile of A549 lung cancer cells, using both 2D and 3D culture models. TDCPP and TPhP significantly reduced cell viability, while TBOEP caused the highest increase in reactive oxygen species (ROS), followed by TPhP, TDCPP, and TCP. Moreover, TPhP, TDCPP, EHDPhP, and TBOEP also elevated the levels of pro-inflammatory cytokine interleukin-8 (IL-8). The lipidomic analysis of 3D cell spheroids exposed to OPFRs for 72 h revealed distinct lipid profiles for each compound at low (25 μM) and high (100 μM) doses. Common features were observed, particularly at high doses, including significant increases in triacylglycerol, diacylglycerol, ceramide, ether-linked phosphatidylethanolamine, and phosphatidylinositol species. These effects were generally more pronounced for TPhP, TDCPP, EHDPhP, TCP, and TBOEP. The accumulation of triglycerides, indicative of augmented energy storage, was confirmed by the visualization of lipid droplets formation. Results suggest disruptions in key toxicological pathways, including oxidative stress, inflammatory signaling (IL-8 upregulation), and apoptosis (ceramide accumulation), all implicated in lung diseases, such as COPD and fibrosis. These results provide a basis for assessing the health risks associated with OPFRs, highlighting the need for further research on chronic low-dose exposure levels.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"270 ","pages":"Article 105508"},"PeriodicalIF":3.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Structural characterization of cholesterol-rich nanoemulsion (LDE) and associates” [Chem. Phys. Lipids 263 (2024) 105418]","authors":"Aline S. Perez ,&nbsp;Aleksandra T. Morikawa ,&nbsp;Raul C. Maranhao ,&nbsp;Antonio M. Figueiredo Neto","doi":"10.1016/j.chemphyslip.2025.105498","DOIUrl":"10.1016/j.chemphyslip.2025.105498","url":null,"abstract":"","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"270 ","pages":"Article 105498"},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid membrane behavior of nitro-fatty acids and their loading into liposomes to activate Nrf2 pathway in RAW264.7 cells with impact on intracellular NO production","authors":"Martina Zatloukalova ,&nbsp;Gabin Fabre ,&nbsp;Lukas Jedinak ,&nbsp;Jiří Pospíšil ,&nbsp;Damian Dziubak ,&nbsp;Aleksandra Pavićević ,&nbsp;Zdenek Dostal ,&nbsp;Jiri Vrba ,&nbsp;Slawomir Sek ,&nbsp;Miloš Mojović ,&nbsp;Patrick Trouillas ,&nbsp;Jan Vacek","doi":"10.1016/j.chemphyslip.2025.105497","DOIUrl":"10.1016/j.chemphyslip.2025.105497","url":null,"abstract":"<div><div>Nitro-fatty acids (NO₂-FAs) are endogenous electrophilic signalling modulators, and some of them have been proposed as drug candidates. The main ones include nitro-oleic acid (NO₂-OA) and other derivatives of unsaturated fatty acids such as nitro-linoleic acid (NO₂-LA). In this study, we describe the behavior of 9/10-NO₂-OA, 10-NO₂-LA and the conjugated nitro-linoleic acid (9/12-NO₂-cLA) in a model POPC (1-palmitoyl-2-oleoyl-<em>sn</em>-glycero-3-phosphocholine) membrane using molecular dynamics and selected experimental approaches. We showed that when loaded in liposomes, NO₂-FAs undergo degradation (a decay reaction) to a very limited extent, in contrast to the free molecular form in an aqueous environment. This was confirmed by the electron paramagnetic resonance spectroscopic analysis of NO radical release. In general, NO₂-FAs suppress membrane hydration, especially in the segment where the ester groups are located. Further, in the presence of NO₂-FAs, there is increased membrane fluidity and a decrease in the degree of lipid order. These effects are greater for NO₂-FAs than for their non-nitrated versions. The presence of a nitro group in close contact with the polar head groups was confirmed. This drives the tilt of the lipid chain which in turn induces membrane disorder. Protonated NO₂-FAs penetrated more easily/deeper into the membrane structure than the dissociated forms and this makes the membrane bilayer surface more negatively charged based on zeta potential measurement. We also found that NO₂-FAs incorporated into POPC liposomes retained their ability to activate the Nrf2 pathway. This was documented by an increased expression of heme oxygenase-1 at the level of mRNA, with a parallel decrease in protein levels of Keap1, in murine macrophage RAW264.7 cells. The NO₂-FAs treatment resulted in an increase in intracellular NO level <em>in vitro</em> as determined by a genetically encoded G-geNOp sensor. This was confirmed at statistically significant level only for NO₂-OA, not for NO₂-LA or NO₂-cLA. The results indicate that biologically relevant NO release may be strictly dependent on which NO₂-FA is investigated. This study supports the hypothesis that NO₂-FAs are distributed (co-localized) in cells and tissues in the lipid or aqueous phase, which affects whether they are mobile, stable, and thus biologically active.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"270 ","pages":"Article 105497"},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the Lipid-POI connection: The mediating role of inflammatory factors","authors":"Tingyu Lang ,&nbsp;Shaoqi Hua ,&nbsp;Xiaolei Liang ,&nbsp;Yongxiu Yang","doi":"10.1016/j.chemphyslip.2025.105495","DOIUrl":"10.1016/j.chemphyslip.2025.105495","url":null,"abstract":"<div><div>POI is a highly heterogeneous, multifactorial condition, and dysregulated lipid metabolism has been implicated in its inflammatory pathogenesis This study is the first to systematically investigate causal relationships between 179 lipid species, 91 inflammatory factors, and POI using Two-Sample Mendelian Randomization (TSMR) and Multivariable Mendelian Randomization (MVMR). By integrating lipidomics and inflammatories data with POI from Genome-wide association study (GWAS) and FinnGen, we identified 18 causally significant lipids, including risk-elevating phosphatidylcholines and sphingomyelins, and protective triglycerides. Methodologically, we innovatively applied Bayesian Weighted Mendelian Randomization (BWMR) to confirm the robustness of causal estimates, addressing limitations of conventional MR in pleiotropy-prone metabolic networks. Biologically, we discovered IL-10 mediates 7.02–9.03 % of the effects of sphingomyelin (d40:2) and (d42:2) on POI, reconciling lipid-driven inflammation with ovarian aging—a mechanism previously unreported. Sensitivity analyses confirmed no horizontal pleiotropy (p &gt; 0.05). This work establishes three advances: (1) First MR evidence linking specific lipid subclasses (not just broad categories) to POI; (2) Identification of IL-10 as a novel inflammatory mediator bridging sphingolipids and POI pathogenesis; (3) A validated framework combining MVMR and mediation analysis to disentangle direct/indirect effects in reproductive aging. Our findings provide clinically actionable insights: IL-10 emerge as potential biomarkers, while triglycerides highlight dietary/therapeutic targets. This mechanistic clarity advances POI research beyond prior observational associations into causal biology.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"269 ","pages":"Article 105495"},"PeriodicalIF":3.4,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol´s role in membrane organization and nicotinic acetylcholine receptor function: Implications for aging and Alzheimer's disease","authors":"Daniel A. Peñalva,&nbsp;Juan Pablo Munafó,&nbsp;Silvia S. Antollini","doi":"10.1016/j.chemphyslip.2025.105484","DOIUrl":"10.1016/j.chemphyslip.2025.105484","url":null,"abstract":"<div><div>Biological membranes are complex entities composed of various molecules exhibiting lateral and transbilayer lipid asymmetries, along with a selective spatial distribution of different membrane proteins. This dynamic orchestration is crucial for proper physiological functions, undergoes changes with aging, and is disturbed in several neurological disorders. In this review, we analyze the impact of disruption in this equilibrium on physiological aging and the onset of pathological conditions. Alzheimer´s disease (AD) is a multifactorial neurodegenerative disorder in the elderly, characterized by the increased presence of the Aβ peptide, which supports the amyloid hypothesis of the disease. However, AD also involves a progressive loss of cholinergic innervation, leading to the cholinergic hypothesis of the disease. Nicotinic acetylcholine receptors (nAChRs) are transmembrane proteins, and Aβ peptides, their oligomeric and fibrillar species, which increase in hydrophobicity as they develop, interact with membranes. Therefore, a membrane hypothesis of the disease emerges as a bridge between the other two. Here, we discuss the impact of the membrane environment, through direct or indirect mechanisms, on cholinergic signaling and Aβ formation and subsequent incorporation into the membrane, with a special focus on the crucial role of cholesterol in these processes.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"269 ","pages":"Article 105484"},"PeriodicalIF":3.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}