title: Liposomes functionalized with acidic lipids rescue Aβ-induced toxicity in murine neuroblastoma cells.
abstract: The loss of synapses and neurons in Alzheimer's disease (AD) is thought to be at least partly induced by toxic species formed by the amyloid beta (Aβ) peptide; therefore, therapeutics aimed at reducing Aβ toxicity could be of clinical use for treatment of AD. Liposomes are suitable vehicles for therapeutic agents and imaging probes, and a promising way of targeting the various Aβ forms. We tested liposomes functionalized with phosphatidic acid, cardiolipin, or GM1 ganglioside, previously shown to have high Aβ-binding capacity. Mimicking Aβ-induced toxicity in mouse neuroblastoma cell lines, combined with administration of cell viability-modulating agents, we observed that functionalized liposomes rescued cell viability to different extents. We also detected rescue of the imbalance of GSK-3β and PP2A activity, and reduction in tau phosphorylation. Thus, these liposomes appear particularly suitable for implementing further therapeutic strategies for AD.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, KI-Alzheimer Disease Research Center (KI-ADRC) Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erika
authors.initials: E
authors.lastname: Bereczki
authors.forename: Francesca
authors.initials: F
authors.lastname: Re
authors.forename: Massimo E
authors.initials: ME
authors.lastname: Masserini
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Jin Jing
authors.initials: JJ
authors.lastname: Pei
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002308:Cardiolipins / Q000009:adverse effects / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005677:G(M1) Ganglioside / Q000009:adverse effects / Q000737:chemistry*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008081:Liposomes / Q000009:adverse effects / Q000737:chemistry*; D051379:Mice; D010712:Phosphatidic Acids / Q000009:adverse effects / Q000737:chemistry*; D010766:Phosphorylation / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002308:Cardiolipins; D008081:Liposomes; D010712:Phosphatidic Acids; D016875:tau Proteins; D005677:G(M1) Ganglioside; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D002265:Carboxylic Ester Hydrolases; C119357:protein phosphatase methylesterase-1