Abstract
Ganglioside GM1 is the most common brain ganglioside enriched in plasma membrane regions known as lipid rafts or membrane microdomains. GM1 participates in many modulatory and communication functions associated with the development, differentiation, and protection of neuronal tissue. It has, however, been demonstrated that GM1 plays a negative role in the pathophysiology of Alzheimer’s disease (AD). The two features of AD are the formation of intracellular neurofibrillary bodies and the accumulation of extracellular amyloid β (Aβ). Aβ is a peptide characterized by intrinsic conformational flexibility. Depending on its partners, Aβ can adopt different spatial arrangements. GM1 has been shown to induce specific changes in the spatial organization of Aβ, which lead to enhanced peptide accumulation and deleterious effect especially on neuronal membranes containing clusters of this ganglioside. Changes in GM1 levels and distribution during the development of AD may contribute to the aggravation of the disease.
Highlights
Alzheimer0 s disease (AD) is the most common neurodegenerative disorder responsible for 70% of all dementia cases [1]
Molecular dynamics simulations demonstrated amyloid β (Aβ) monomers binding to the dimyristoyl-phosphatodylcholine (DM-PC) bilayer that leads to structural transition by forming stable helix structure in its C-terminal, which penetrates into the bilayer hydrophobic core [73]
Computational modeling and molecular dynamics (MD) studies revealed that cholesterol induces higher β-sheet content in the Aβ peptide oligomers, which may lead to faster fibril formation [93]
Summary
Alzheimer0 s disease (AD) is the most common neurodegenerative disorder responsible for 70% of all dementia cases [1]. Direct effects of Aβ on lipid bilayer, and changes in activities of membrane-bound receptors and channels have been observed in brains of AD patients and model animals. The cholinergic system including acetylcholine production, synaptic release and degradation, as well as acetylcholine interaction with nicotinic and G protein-coupled receptors, is a crucial player in the development of AD [22,23]. Specific Aβ-lipid recognition plays a role, where cholesterol, sphingomyelin, and ganglioside GM1 are supposed to be the most important factors regulating Aβ–membrane binding [10,34,35] Such interactions may have impact on Aβ secondary, tertiary, and quaternary structure that play a role in enhancing Aβ peptide cytotoxicity [10,16,36]
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