9-Methylfascaplysin Prevents Neuroinflammation and Synaptic Damage via Cell-Specific Inhibition of Kinases in APP/PS1 Transgenic Mice.

ABSTRACT:

Background

Alzheimer's disease (AD) is a leading neurodegenerative disorder without effective treatments. The nonlinear dynamic nature of AD pathophysiology suggested that multiple pharmacological actions of anti-AD drugs should be elucidated. 9-Methylfascaplysin (9-MF) was previously designed and synthesized as a novel anti-AD candidate.

Methods and results

In this study, 9-MF at low concentrations significantly prevented cognitive impairments with similar efficacy as donepezil in APP/PS1 transgenic mice. In addition, 9-MF potently reduced β-amyloid (Aβ)-associated neuroinflammation and tau-associated synaptic damage in vivo. 9-MF-regulated microglia-specific differentially phosphorylated proteins (DPPs) were mainly enriched in neuroinflammation, while 9-MF-regulated neuron

SUBMITTER: Le J 

PROVIDER: S-EPMC11576489 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature