Rapamycin suppresses Aβ_25-35- or LPS-induced neuronal inflammation via modulation of NF-κB signaling

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Neuroinflammation is a key factor in Alzheimer's disease (AD) pathogenesis.
• Mammalian target of rapamycin (mTOR) signaling is implicated in neuroinflammation.

Purpose of the Study:

• To investigate the anti-inflammatory effects of Rapamycin (RAPA) in Alzheimer's disease models.
• To elucidate the underlying mechanisms of RAPA's action on neuroinflammation.

Main Methods:

• Utilized in vivo and in vitro models of AD, including amyloid-beta (Aβ) and lipopolysaccharide (LPS) treatments.
• Assessed the expression of key inflammatory markers and signaling proteins (mTOR, NF-κB, TNF-α, IL-1β, Bax).
• Examined the effect of RAPA on the nuclear translocation of mTOR and NF-κB.

Main Results:

• Amyloid-beta induced significant neuronal inflammation and increased mTOR activity.
• RAPA administration downregulated mTOR, p-mTOR, NF-κB p65, p-p65, TNF-α, IL-1β, and Bax protein expression.
• RAPA inhibited the nuclear translocation of mTOR and NF-κB.

Conclusions:

• Rapamycin exhibits significant anti-inflammatory properties in AD models.
• RAPA exerts its neuroprotective effects by suppressing mTOR signaling and reducing NF-κB nuclear import.
• These findings highlight RAPA as a potential therapeutic agent for Alzheimer's disease.