Lysozyme Aggregates Induce Apoptosis and Necroptosis in Adipose Mesenchymal Stem Cells

Alzheimer's disease is the most common form of neurodegenerative disease that causes gradual loss of memory, learning and cognition. One of the hypotheses justifying the cause of this disease is the amyloid cascade hypothesis. Based on this hypothesis, “incorrect” proteolytic hydrolysis of amyloid precursor protein (APP), leads to generation of beta amyloid peptide and its subsequent aggregation. Accumulation of extracellular amyloid beta protein causes loss of synaptic connections and demise of neurons in the hippocampus region of the brain. So far, drug treatments only reduce symptoms of the disease, and none of them lead to a complete recovery of the disease. Utilizing stem cells seems to be a suitable therapeutic approach due to their potential for differentiation, proliferation and survival. In this research, we aimed to investigate the effect of lysozyme (as a model protein in protein aggregation research) protein aggregates on human adipose mesenchymal stem cells (AMSCs), considered as a promising candidate for stem cell therapy, and the SH-SY5Y cell line, utilized as a neuronal cellular model. To achieve this objective, the aggregates of lysozyme were prepared and characterized using various analytical techniques. Subsequently, AMSCs and SH-SY5Y cells were treated with monomeric and aggregated forms of lysozyme, and their effect was examined through a series of assays evaluating cellular morphology, viability, cell cycle progression, and the production rate of reactive oxygen species (ROS). The results confirmed that the monomeric forms of proteins were not harmful to the cell lines, while the aggregates reduced viability and cause cell death. Interestingly, SH-SY5Y cell line indicated apoptosis and necroptosis cell death while there was a slight apoptotic cell death in AMSCs post-treatment. Therefore, it seems that AMSCs could be considered as a promising stem cell system for cell therapy alongside utilizing apoptosis inhibitors.