Related Experiment Video
Updated: Aug 20, 2026

Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
Published on: June 26, 2018
Annular alpha-synuclein oligomers are potentially toxic agents in alpha-synucleinopathy. Hypothesis
Dean L Pountney1, Nicolas H Voelcker, Wei Ping Gai
1Department of Human Physiology and School of Chemistry, Physics and Earth Sciences, Flinders University, Bedford Park SA 5042, Australia.
Abstract:
Recently, we demonstrated that soluble 30-50 nm-sized annular alpha-synuclein oligomers are released by mild detergent treatment from glial cytoplasmic inclusions (GCIs) purified from multiple system atrophy brain tissue (Pountney et al., J. Neurochem. 90:502, 2004). Dynamic antibody recognition imaging using a specific anti-alpha-synuclein antibody confirmed that the annular structures were positive for alpha-synuclein. This showed that pathological alpha-synucleinopathy aggregates can be a source of annular alpha-synuclein species. In contrast to pathological alpha-synuclein, recombinant alpha-synuclein yielded only spherical oligomers after detergent treatment, indicating a greater propensity of the pathological protein to form stable annular oligomers. In vitro, we found that Ca2+ binding to monomeric alpha-synuclein, specifically amongst a range of different metal ions, induced the rapid formation of annular oligomers (Lowe et al., Protein Sci.,13:3245, 2004). Hence, alpha-synuclein speciation may also be influenced by the intracytoplasmic Ca2+ concentration. We also showed that annular alpha-synuclein oligomers can nucleate filament formation. We hypothesize that soluble alpha-synuclein annular oligomers may be cytotoxic species, either by interacting with cell membranes or components of the ubiquitin proteasome system. The equilibrium between alpha-synuclein species may be influenced by intracellular Ca2+ status, interaction with lipid vesicles or other factors.
Related Concept Videos
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Parkinson Disease ll: Pathophysiology
Alzheimer Disease ll: Pathophysiology
Neural Regulation

