# Elucidation of Secondary Structure and Toxicity of α-Synuclein Oligomers and Fibrils Grown in the Presence of Phosphatidylcholine and Phosphatidylserine

## TL;DR

This study explores how phospholipids affect the structure and toxicity of α-synuclein aggregates linked to Parkinson's disease.

## Contribution

The study reveals that phosphatidylcholine and phosphatidylserine alter α-synuclein aggregation rates, structures, and toxicity in neuronal environments.

## Key findings

- Phosphatidylserine accelerates α-synuclein aggregation while phosphatidylcholine inhibits it.
- Both phospholipids modify the secondary structure of α-synuclein aggregates at different aggregation stages.
- α-Syn aggregates formed with phospholipids show higher toxicity and oxidative stress in rat neurons compared to lipid-free aggregates.

## Abstract

Abrupt aggregation of α-synuclein (α-Syn)
in the midbrain
hypothalamus and thalamus is a hallmark of Parkinson’s disease
(PD), the fastest growing neurodegenerative pathology, projected to
strike 12 million people by 2040 worldwide. In this study, we examine
the effect of two phospholipids that are present in neuronal membranes,
phosphatidylcholine (PC) and phosphatidylserine (PS), on the rate
of α-Syn aggregation. We found that PS accelerated α-Syn
aggregation, whereas PC strongly inhibited α-Syn aggregation.
We also utilized the nano-infrared imaging technique, also known as
atomic force microscopy infrared (AFM-IR) spectroscopy, to investigate
whether PC and PS only change the rates or also modify the secondary
structure of α-Syn aggregates. We found that both phospholipids
uniquely altered the secondary structure of α-Syn aggregates
present at the lag and growth phase, as well as the late stage of
protein aggregation. In addition, compared to the α-Syn aggregates
formed in the lipid-free environment, α-Syn:PC and α-Syn:PS
aggregates demonstrated higher cellular toxicity to N27 rat neurons.
Interestingly, both α-Syn:PC and α-Syn:PS aggregates showed
similar levels of oxidative stress, but α-Syn:PC aggregates
exhibited a greater degree of mitochondrial dysfunction compared to
α-Syn:PS aggregates.