Exogenous Amyloid\nFibrils Can Cause Significant Upregulation\nof Neurodegenerative Disease Proteins

Neurodegenerative diseases, such as Alzheimer’s\ndisease\nand Parkinson’s disease, are associated with the formation\nof amyloid fibrils. In familial cases, the mutant causative genes\naccentuate disease progression through overexpression or misfolding\nof amyloidogenic proteins. Besides, considerable amyloidosis cases\narise from external factors, but their origin and mechanisms are not\nyet fully understood. Herein, we found that amyloid fibrils generated\nfrom egg and milk proteins, in addition to their nutritional effects\nto intestinal cells, can selectively reduce the viability of nervous\ncells as well as pancreatic islet cells. In contrast, soy protein\namyloid fibrils lacked cytotoxicity to the aforementioned cells. This\nprotein source and cell type-dependent cytotoxicity are demonstrated\nto be associated with the significant upregulation of amyloidogenic\nproteins. The finding was also confirmed by the vein injection of\nbeta-lactoglobulin fibrils to mice, exhibiting the pronounced upregulations\nof amyloid beta<sub>1–42</sub> (Aβ<sub>1–42</sub>) and islet amyloid polypeptide in vivo. The study therefore provides\ninsight into the health implications of exogenous amyloid fibrils.