Membranes, Год журнала: 2024, Номер 14(11), С. 231 - 231

Опубликована: Ноя. 6, 2024

The transition of peptides or proteins along a misfolding continuum from soluble functional states to pathological aggregates, ultimately deposit as amyloid fibrils, is process that underlies an expanding group human diseases-collectively known protein-misfolding disorders (PMDs). These include common and debilitating conditions, such Alzheimer's disease, Parkinson's type-2 diabetes. Compelling evidence has emerged the complex interplay between misfolded biological membranes key determinant pathogenic mechanisms by which harmful entities are formed exert their cytotoxicity. Most efforts thus far develop disease-modifying treatments for PMDs have largely focused on anti-aggregation strategies: neutralise, prevent formation of, toxic species. Herein, we review critical role phospholipid membrane in mediating enabling pathogenicity. We consequently propose development small molecules, potential uniquely modify physicochemical properties make it more resilient against damage proteins, could provide novel therapeutic approach PMDs. By way example, natural compounds shown intercalate into lipid bilayers inhibit amyloid-lipid interactions, aminosterols, squalamine trodusquamine, cholesterol, ubiquinone, select polyphenols, discussed. Such strategy would counter wide range biomolecules implicit numerous pathologies.

Язык: Английский