FLZ attenuates learning and memory deficits via suppressing neuroinflammation induced by LPS in mice

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder in which neuroinflammation plays an important role. FLZ is a novel synthetic derivative of natural squamosamide. Previous studies demonstrated that FLZ had neuroprotective effects on AD models and showed strong anti-inflammatory property in Parkinson's disease models. However, whether the neuroprotective effects of FLZ on AD are associated with its anti-inflammatory property is still not fully elucidated. In this study, we aimed to investigate the ability of FLZ in modulating inflammation. The results showed that FLZ significantly improved memory deficits and alleviated neuronal damage as well as neuronal loss in the hippocampus of mice intracerebroventricular injected with lipopolysaccharide (LPS). Mechanistic studies revealed that the neuroprotective effects of FLZ were due to the suppression of neuroinflammation induced by LPS, as indicated by inactivation of astrocytes and microglia, reduced production of tumor necrosis factor-α, interleukin-1β, and nitric oxide, as well as decreased expression of cyclooxygenase-2 and inducible nitric oxide synthase. The beneficial effects of FLZ on AD were further supported by the finding that FLZ attenuated β-amyloid production through inhibiting β-amyloid precursor protein cleaving enzyme 1 expression. These results suggested that anti-inflammatory agent could be useful for the treatment of AD.

Keywords::

• Alzheimer's disease
• FLZ
• lipopolysaccharide
• neuroinflammation
• β-amyloid

Acknowledgments

This work was financially supported by grants from Fundamental Research Funds for the Central Universities [grant number 2012S08], Beijing NOVA Program [grant number 2011109], PUMC Youth Fund [grant number 2012J19], [grant number 3332013111], and supported by Program for New Century Excellent Talents in University [grant number 3332013128].

Disclosure statement

No potential conflict of interest was reported by the author(s).

Notes

^1. Co-first author, equal contribution.