PROVIDE NEW INSIGHTS IN ALPHA-SYNUCLEIN INDUCED CELL MEMBRANE DISRUPTION USING SCANNING ION CONDUCTANCE MICROSCOPY AND SURFACE PLASMON RESONANCE MICROSCOPY

NIH RePORTER · NIH · R15 · $438,000 · view on reporter.nih.gov ↗

Abstract

Abstract: Parkinson’s disease (PD) is a leading neurodegenerative disorder attributed to the abnormal folding and aggregation of alpha-synuclein (α-syn) in dopaminergic neurons. The exact causative mechanism, however, remains unclear. Leveraging advanced techniques like scanning ion conductance microscopy (SICM) and surface plasmon resonance microscopy (SPRM), our previous work elucidated how α-synuclein oligomers might compromise neuronal membranes, while pre-formed fibrils (PFFs) primarily influence membrane roughness without inducing significant cytotoxicity. This new phase aims to deepen our understanding by exploring the role of phosphorylated α-syn (P-syn), a pathological variant of α-syn. The objectives include synthesizing and characterizing P-syn, assessing its impact on neuronal membranes, and evaluating its influence on iron-driven dopamine oxidation. Furthermore, we will investigate the role of environmental toxins, specifically nanoplastics, in α-syn aggregation and its subsequent interactions with membranes. The outcomes from this research are anticipated to shed light on the molecular intricacies of PD and potentially pave the way for targeted therapeutic strategies.

Key facts

NIH application ID
10974782
Project number
2R15NS120157-02
Recipient
CALIFORNIA STATE UNIVERSITY LOS ANGELES
Principal Investigator
Yixian Wang
Activity code
R15
Funding institute
NIH
Fiscal year
2024
Award amount
$438,000
Award type
2
Project period
2020-09-30 → 2027-08-31