α S1 -Casein-Loaded Proteo-liposomes as Potential Inhibitors in Amyloid Fibrillogenesis: In Vivo Effects on a C. elegans Model of Alzheimer's Disease.
Angela PaternaPamela SantonicolaGiulia Di PrimaEstella RaoSamuele RaccostaGiuseppina ZampiClaudio RussoOscar MoranMauro MannoElia Di SchiaviFabio LibrizziRita CarrottaPublished in: ACS chemical neuroscience (2023)
According to the amyloid hypothesis, in the early phases of Alzheimer's disease (AD), small soluble prefibrillar aggregates of the amyloid β-peptide (Aβ) interact with neuronal membranes, causing neural impairment. Such highly reactive and toxic species form spontaneously and transiently in the amyloid building pathway. A therapeutic strategy consists of the recruitment of these intermediates, thus preventing aberrant interaction with membrane components (lipids and receptors), which in turn may trigger a cascade of cellular disequilibria. Milk α s1 -Casein is an intrinsically disordered protein that is able to inhibit Aβ amyloid aggregation in vitro , by sequestering transient species. In order to test α s1 -Casein as an inhibitor for the treatment of AD, it needs to be delivered in the place of action. Here, we demonstrate the use of large unilamellar vesicles (LUVs) as suitable nanocarriers for α s1 -Casein. Proteo-LUVs were prepared and characterized by different biophysical techniques, such as multiangle light scattering, atomic force imaging, and small-angle X-ray scattering; α s1 -Casein loading was quantified by a fluorescence assay. We demonstrated on a C. elegans AD model the effectiveness of the proposed delivery strategy in vivo . Proteo-LUVs allow efficient administration of the protein, exerting a positive functional readout at very low doses while avoiding the intrinsic toxicity of α s1 -Casein. Proteo-LUVs of α s1 -Casein represent an effective proof of concept for the exploitation of partially disordered proteins as a therapeutic strategy in mild AD conditions.
Keyphrases
- drug delivery
- high resolution
- randomized controlled trial
- oxidative stress
- cognitive decline
- single molecule
- systematic review
- sensitive detection
- risk assessment
- computed tomography
- amino acid
- binding protein
- climate change
- brain injury
- human health
- living cells
- fluorescent probe
- genetic diversity
- wound healing
- smoking cessation
- human serum albumin