Alzheimer's disease (AD) is the most prevalent form of age-related dementia, preceded by a prodromal period. The key pathological factor of AD is chronic excessive brain amyloid-beta (Aβ) aggregation, and it occurs much before the initial symptoms of AD. It has been reported that chronic neuroinflammation exists during and after the prodromal period due to the presence of chronic excessive brain Aβ aggregation, which may breach the blood-brain barrier (BBB), leading to a prodromal surge of inflammatory mediators in the brain. During AD, there is also an increased concentration of Aβ in the peripheral circulation, which may lead to systemic inflammation through the activation of immune cells. The activation of peripheral systemic inflammation may also play an important role in the aggravation of neuroinflammation during AD progression. However, the possible roles of peripheral blood mononuclear cells (PBMCs), including immune cells, are mostly unclear in AD progression. Interleukin-17A (IL-17A) is significantly released by PBMCs and is also associated with the progression of AD pathology. This study aimed to evaluate the protective role of Chrysin in Aβ (Aβ25-35)-mediated IL-17A-IL-17 receptor A (IL-17RA) downstream signalling in rat PBMCs. Aβ exposure stimulated the release of IL-17A and triggered enhanced downstream signalling through IL-17RA activation. The results revealed a protective role of Chrysin in alleviating the level of IL-17A and its downstream proinflammatory signalling mediated through IL-17RA activation.
Gautam et al. (Tue,) studied this question.