# Higher Purity of Phosphatidylserine Improves Human Cortical Neuron Function by Modulating SIRT1-PGC-1α Pathways

## TL;DR

Higher purity phosphatidylserine improves human cortical neuron function by boosting SIRT1 and PGC-1α, which protect neurons and support mitochondrial health.

## Contribution

This study is the first to show that PS purity modulates SIRT1-PGC-1α pathways in human neurons, offering new insights into neuroprotection.

## Key findings

- 80% pure PS significantly increases SIRT1 and PGC-1α levels in human cortical neurons.
- PS treatment counteracts Aβ42-induced cytotoxicity and preserves SIRT1 and PGC-1α in an Alzheimer’s disease model.
- PS-induced PGC-1α upregulation is dependent on SIRT1 activity.

## Abstract

While phosphatidylserine (PS) is recognized for its neuroprotective properties, the effects of PS purity on human cortical neurons remain unexplored. This study investigates the effects of three different PS purities (15 µM of 50%, 70%, and 80%) on neuronal health using human-embryonic-stem-cell-derived cortical neurons. Our findings reveal that higher PS purity enhances the expression of key regulatory proteins Sirtuin 1 (SIRT1) and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), known for their roles in neuroprotection and mitochondrial function. Specifically, 80% PS purity significantly increases SIRT1 and PGC-1α levels, suggesting that PS purity strengthens neuroprotective pathways and improves mitochondrial quality control. Through SIRT1 knockdown experiments, we demonstrate that PS-induced upregulation of PGC-1α is SIRT1 dependent, highlighting a SIRT1-PGC-1α regulatory axis that enhances mitochondrial health. In an amyloid-beta 1–42 (Aβ42)-induced Alzheimer’s disease (AD) model, PS treatment reduced cytotoxicity and countered the Aβ42-induced downregulation of SIRT1 and PGC-1α, particularly at 70% and 80% PS purity, indicating PS’s role in preserving neuronal viability and combating AD-like pathology. These results suggest that the biological activity of PS preparations in vitro can depend on purity, motivating future studies to define compositional determinants and bioavailability relevant to translational applications.