Related Experiment Video
Updated: Jan 28, 2026

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
Published on: November 25, 2022
Cyclized NDGA modifies dynamic α-synuclein monomers preventing aggregation and toxicity
Malcolm J Daniels1, J Brucker Nourse2, Hanna Kim2
1Pharmacology Graduate Group, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
None:
Growing evidence implicates α-synuclein aggregation as a key driver of neurodegeneration in Parkinson's disease (PD) and other neurodegenerative disorders. Herein, the molecular and structural mechanisms of inhibiting α-synuclein aggregation by novel analogs of nordihydroguaiaretic acid (NDGA), a phenolic dibenzenediol lignan, were explored using an array of biochemical and biophysical methodologies. NDGA analogs induced modest, progressive compaction of monomeric α-synuclein, preventing aggregation into amyloid-like fibrils. This conformational remodeling preserved the dynamic adoption of α-helical conformations, which are essential for physiological membrane interactions. Oxidation-dependent NDGA cyclization was required for the interaction with monomeric α-synuclein. NDGA analog-pretreated α-synuclein did not aggregate even without NDGA-analogs in the aggregation mixture. Strikingly, NDGA-pretreated α-synuclein suppressed aggregation of naïve untreated aggregation-competent monomeric α-synuclein. Further, cyclized NDGA reduced α-synuclein-driven neurodegeneration in Caenorhabditis elegans. The cyclized NDGA analogs may serve as a platform for the development of small molecules that stabilize aggregation-resistant α-synuclein monomers without interfering with functional conformations yielding potential therapies for PD and related disorders.
Related Concept Videos
Cancer Prevention
Some...
Intramolecular Claisen Condensation of Dicarboxylic Esters: Dieckmann Cyclization
Prevention of Further Absorption of Poison
Preventive Healthcare Services
Aggregates Classification
Petrographic classification groups aggregates based on common mineralogical characteristics. Some of the common mineral groups found in aggregates are...
Toxic Reactions: Overview
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...

