ArticleFrontiers in physiology2013
Cholesterol accelerates the binding of Alzheimer's β-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation.
Article in Frontiers in physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 99 citations in OpenAlex.
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- Molecular mechanisms at the basis of the protective effect exerted by EPPS on neurodegeneration induced by prefibrillar amyloid oligomers.Scientific reports · 2024Article
- Emerging role of MAPK signaling in glycosphingolipid-associated tumorigenesis.Glycoconjugate journal · 2024Review
- Membrane Interaction Characteristics of the RTX Toxins and the Cholesterol-Dependence of Their Cytolytic/Cytotoxic Activity.International journal of molecular sciences · 2024Review
- Sugar distributions on gangliosides guide the formation and stability of amyloid-β oligomers.Biophysical chemistry · 2023Article
- Molecular Biophysics of Class A G Protein Coupled Receptors-Lipids Interactome at a Glance-Highlights from the ABiomolecules · 2023Review
- Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts: Lessons for the Future.International journal of molecular sciences · 2023Review
- AmyP53 Prevents the Formation of Neurotoxic β-Amyloid Oligomers through an Unprecedent Mechanism of Interaction with Gangliosides: Insights for Alzheimer's Disease Therapy.International journal of molecular sciences · 2023Article
- Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases.Frontiers in aging neuroscience · 2023Review
- AmyP53, a Therapeutic Peptide Candidate for the Treatment of Alzheimer's and Parkinson's Disease: Safety, Stability, Pharmacokinetics Parameters and Nose-to Brain Delivery.International journal of molecular sciences · 2022Article
- TRPV1 in male reproductive system: focus on sperm function.Molecular and cellular biochemistry · 2022Review
- Specific Mutations in the Cholesterol-Binding Site of APP Alter Its Processing and Favor the Production of Shorter, Less Toxic Aβ Peptides.Molecular neurobiology · 2022Article
- Current understandings and perspectives of petroleum hydrocarbons in Alzheimer's disease and Parkinson's disease: a global concern.Environmental science and pollution research international · 2022Review
- Therapeutic Uses of Bacterial Subunit Toxins.Toxins · 2021Review
- Aβ Beyond the AD Pathology: Exploring the Structural Response of Membranes Exposed to Nascent Aβ Peptide.International journal of molecular sciences · 2020Article
- Metabolism of Glycosphingolipids and Their Role in the Pathophysiology of Lysosomal Storage Disorders.International journal of molecular sciences · 2020Review
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- Synergistic antiviral effect of hydroxychloroquine and azithromycin in combination against SARS-CoV-2: What molecular dynamics studies of virus-host interactions reveal.International journal of antimicrobial agents · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Age-related alterations of membrane lipids in brain cell membranes together with high blood cholesterol are considered as major risk factors for Alzheimer's disease. Yet the molecular mechanisms by which these factors increase Alzheimer's risk are mostly unknown. In lipid raft domains of the plasma membrane, neurotoxic Alzheimer's beta-amyloid (Abeta) peptides interact with both cholesterol and ganglioside GM1. Recent data also suggested that cholesterol could stimulate the binding of Abeta to GM1 through conformational modulation of the ganglioside headgroup. Here we used a combination of physicochemical and molecular modeling approaches to decipher the mechanisms of cholesterol-assisted binding of Abeta to GM1. With the aim of decoupling the effect of cholesterol on GM1 from direct Abeta-cholesterol interactions, we designed a minimal peptide (Abeta5-16) containing the GM1-binding domain but lacking the amino acid residues involved in cholesterol recognition. Using the Langmuir technique, we showed that cholesterol (but not phosphatidylcholine or sphingomyelin) significantly accelerates the interaction of Abeta5-16 with GM1. Molecular dynamics simulations suggested that Abeta5-16 interacts with a cholesterol-stabilized dimer of GM1. The main structural effect of cholesterol is to establish a hydrogen-bond between its own OH group and the glycosidic-bond linking ceramide to the glycone part of GM1, thereby inducing a tilt in the glycolipid headgroup. This fine conformational tuning stabilizes the active conformation of the GM1 dimer whose headgroups, oriented in two opposite directions, form a chalice-shaped receptacle for Abeta. These data give new mechanistic insights into the stimulatory effect of cholesterol on Abeta/GM1 interactions. They also support the emerging concept that cholesterol is a universal modulator of protein-glycolipid interactions in the broader context of membrane recognition processes.
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