2022 Volume 9 Issue 3 Pages 135-145
The physiological role of amyloid-β (Aβ) is unknown, while it plays an important role in the onset and progression of Alzheimer's disease (AD). Aβ polymerization leads to enhanced neurotoxicity, persistent degradation, and deposition in the brain, resulting in decreased Aβ clearance. Diabetes mellitus and poor sleep quality are representative risk factors for the development of AD. Methylglyoxal (MGO) and acrolein are increased in diabetic patients, a representative disease with high glycative stress, and melatonin secretion is decreased during poor sleep quality. In this study, we focused on the Aβ phagocytosis of microglia, which plays a role in Aβ clearance, and examined the effects of Aβ glycation and melatonin. Glycated Aβ was prepared by MGO or acrolein treatment. Fluorescently labeled TAMRA-Aβ and primary rat microglial cells (Cosmo Bio) were used in the experiments. Several new findings were obtained from this experiment. First, microglia phagocytose Aβ, while their phagocytic capacity for glycated Aβ was markedly reduced. Second, Aβ phagocytosis was enhanced by melatonin. Concurrently, spontaneous death of cultured microglia was greater when Aβ was not added than when Aβ was. These findings suggest that prevention of Aβ glycation by countermeasures against glycative stress and prevention of AD progression by lifestyle, i.e., improvement of sleep quality, are important, rather than elimination of Aβ as has been conventionally practiced.
