HEWL interacts with dissipated oleic acid micelles, and decreases oleic acid cytotoxicity

Area of Science:

• Neuroscience
• Biochemistry
• Cell Biology

Background:

• Senile plaques are hallmarks of Alzheimer's Disease (AD), but current treatments targeting tau and beta-amyloid are ineffective.
• Research into AD mechanisms is crucial, with emerging evidence suggesting senile plaques may protect against S100A9-driven inflammation.

Purpose of the Study:

• To investigate the interaction between oleic acid (OA) micelles and hen egg white lysozyme (HEWL).
• To determine if this interaction influences amyloid formation and cellular toxicity.
• To explore potential protective mechanisms against OA-induced cytotoxicity in neural cells.

Main Methods:

• Utilized atomic force microscopy and fluorescence microscopy to observe aggregate formation.
• Co-incubated OA micelles with HEWL to study amyloidogenesis.
• Assessed the protective effects of OA-HEWL co-aggregates on SH-SY5Y cells and mouse neural stem cells against OA toxicity.

Main Results:

• OA micelles interacted with HEWL, promoting amyloid formation.
• HEWL formed round aggregates in the presence of OA micelles, differing from HEWL protofibrils alone.
• Co-aggregation of OA and HEWL formed large clumps that sequestered toxic OA micelles.
• These co-aggregates protected neural cell lines and stem cells from OA toxicity.

Conclusions:

• HEWL amyloid formation is promoted by OA micelles.
• HEWL-OA co-aggregates exhibit a protective function by acting as a sink for toxic OA micelles.
• This mechanism suggests a novel protective role for amyloid formation in mitigating OA cytotoxicity, potentially relevant for neurodegenerative disease research.