Abstract
In the brains of elderly dementia patients, important proteins (i.e., amyloid β [Aβ], tau, and α-synuclein) undergo post-translational modification, polymerization, aggregation, and deposition in tissues. Glycative stress, a non-physiological factor inducing these phenomena, is a state of excess aldehydes, and is induced by hyperglycemia, a high-fat diet, and alcohol consumption. In the lipid-rich brain, concurrently with carbohydrate-derived aldehydes, FA-derived aldehydes generated by the oxidation of FAs modify brain proteins like a double punch. Our previous reports have shown that glycated Aβ can become resistant to microglia phagocytosis and may interfere with clearance. In this study, we created an Aβ phagocytosis evaluation model using microglia-derived BV2 cells and evaluated the effects of mesenchymal stem cell secretome (SCST). SCST contains various growth factors and extracellular vesicles (EVs), and it has been reported that nasal administration improves symptoms in elderly dementia patients. Present results showed that SCST promotes Aβ phagocytosis in a dose-dependent manner. These findings suggest that SCST may activate microglia and contribute to the homeostasis of Aβ clearance. We speculate that it may also be important from the perspective of gliaprotection.
