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 (Aß) peptide; therefore, therapeutics aimed at reducing Aß 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 Aß forms. We tested liposomes functionalized with phosphatidic acid, cardiolipin, or GM1 ganglioside, previously shown to have high Aß-binding capacity. Mimicking Aß-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-3ß and PP2A activity, and reduction in tau phosphorylation. Thus, these liposomes appear particularly suitable for implementing further therapeutic strategies for AD.
Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/antagonists & inhibitors , Cardiolipins/chemistry , G(M1) Ganglioside/chemistry , Liposomes/chemistry , Phosphatidic Acids/chemistry , Amyloid beta-Peptides/chemistry , Animals , Carboxylic Ester Hydrolases/metabolism , Cardiolipins/adverse effects , Cell Line, Tumor , Cell Survival/drug effects , G(M1) Ganglioside/adverse effects , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta , Liposomes/adverse effects , Mice , Phosphatidic Acids/adverse effects , Phosphorylation/drug effects , tau Proteins/metabolismABSTRACT
Anticardiolipin antibody (aCL) screening using an ELISA technique, in 76 patients of Indian origin with systemic lupus erythematosus (SLE), showed aCL in 27.63 per cent of patients. This prevalence was much lower than that reported in the Western population. The presence of aCL showed positive correlations with recurrent abortions and organic neurological lesions seen in SLE.
