Abstract
Neuroinflammation induced by overactivated glia cells is believed to be a major hallmark of Alzheimer's disease (AD) and a hopeful target against AD. A rhamnoside PL201 was previously reported to promote neurogenesis and ameliorate AD, and in this study, we revealed that PL201 also significantly reduced accumulation of the activated microglia and proinflammatory cytokines in APP/PS1 mice. In vitro, PL201 consistently suppressed the microglia induction of proinflammatory cytokines after stimulation with lipopolysaccharides and Aβ42. Further mechanistic studies demonstrated that PL201 considerably enhanced the expression level and the nuclear translocation of Nrf2, a key regulator of neuroinflammation. Moreover, PL201 effectively stimulated Nrf2 signaling cascade, including upregulation of HO-1 and downregulation of NF-κB pathway. Thus, our findings indicated the anti-neuroinflammatory effect by PL201 in vivo and suggested that PL201 or the like, with multiple functions such as neurogenesis, mitochondria maintenance, and anti-neuroinflammation, could be a promising candidate in AD treatment.
Highlights
Alzheimer’s disease (AD) is a chronic neurodegenerative disease and the most common cause of dementia [1]
To investigate whether PL201 treatment affected neuroinflammation in AD mice, we evaluated the microglial reactivity in the hippocampus and cortex by staining with ionized calcium binding adaptor molecule 1 (Iba1) antibody, which is a specific marker of microglia in the brain
We found that the microglia accumulating around the amyloid plagues significantly increased in the hippocampus and cortex of APP/PS1 mice when compared with the WT controls (Figures 1A,B)
Summary
Alzheimer’s disease (AD) is a chronic neurodegenerative disease and the most common cause of dementia [1]. Microglia, which are the major resident immune cells in the central nervous system (CNS), play a critical role in regulating neuroinflammation [5, 6]. As a prominent feature of AD, microglia are recruited to amyloid beta (Aβ) plaques and being activated [7,8,9]. These activated microglia release chemokines, cytokines, and other inflammatory mediators such as IL-1β, IL-6, TNFα, MIP-1α, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), which will further aggravate neuronal damage and AD pathologies [2, 10,11,12]
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