Multi-target neuroprotection by dl-PHPB in APP/PS1 mice: a proteomic analysis.
Yingni Sun1,2,3, Guoliang Bai4, Kangmin Yang5
1School of Life Sciences, Ludong University, Yantai, China.
Frontiers in Pharmacology
|May 9, 2025
Summary
Potassium 2-(1-hydroxypentyl) benzoate (dl-PHPB) shows neuroprotection in Alzheimer's disease (AD) models. This study identified key proteins involved in AD pathology, revealing dl-PHPB's mechanism and potential therapeutic targets.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuropathological hallmarks.
- Potassium 2-(1-hydroxypentyl) benzoate (dl-PHPB) exhibits promising neuroprotective effects in preclinical AD models, but its underlying mechanisms are not fully understood.
Purpose of the Study:
- To elucidate the neuroprotective mechanisms of dl-PHPB in preclinical Alzheimer's disease models.
- To identify potential therapeutic targets for AD by analyzing protein expression changes.
Main Methods:
- Comparative proteomic analysis using two-dimensional difference gel electrophoresis (2D-DIGE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Analysis of protein expression in the cortex and hippocampus of APP/PS1 transgenic mice treated with dl-PHPB or vehicle, compared to wild-type controls.
Main Results:
- Identified differentially expressed proteins in APP/PS1 mice related to energy metabolism, neuronal structure, inflammation, oxidative stress, and amyloid-beta (Aβ) and Tau pathways.
- dl-PHPB treatment modulated the expression of several proteins, restoring cofilin-2 and VDAC1 levels towards normal in treated APP/PS1 mice.
Conclusions:
- dl-PHPB exerts neuroprotection through mechanisms involving the modulation of key proteins implicated in AD pathogenesis.
- Proteins such as cofilin-2 and VDAC1 show potential as therapeutic targets and biomarkers for evaluating treatment efficacy in Alzheimer's disease.
