Acetylcholinesterase as an amyloid enhancing factor in PrP82-146 aggregation process

Area of Science:

• Neuroscience
• Biochemistry
• Molecular Biology

Background:

• Acetylcholinesterase (AChE) is implicated in beta-amyloid plaque formation in the brain.
• AChE has been shown to promote the aggregation of prion protein peptides.
• Amyloid plaques are a hallmark of neurodegenerative diseases like Gerstmann-Sträussler-Scheinker (GSS) disease.

Purpose of the Study:

• To investigate the role of AChE in the fibrillization of PrP82-146, a key component of GSS amyloid plaques.
• To elucidate the mechanism by which AChE influences PrP82-146 aggregation.
• To assess the therapeutic potential of targeting AChE in amyloidogenesis.

Main Methods:

• In vitro fibrillization assays of PrP82-146.
• Monitoring aggregate formation kinetics in relation to AChE concentration.
• Characterization of mature fibrils using tinctorial and optical properties.
• Atomic force microscopy (AFM) to analyze oligomer and fibril formation.
• Inhibition studies using propidium iodide to probe the role of the AChE peripheral site.

Main Results:

• AChE significantly accelerates the fibrillization of PrP82-146.
• The rate of PrP82-146 aggregate formation is directly correlated with AChE concentration.
• Mature fibrils exhibit amyloid properties.
• AChE markedly speeds up oligomer and amyloid fibril formation, as observed by AFM.
• Propidium iodide inhibits the fibrillization process, indicating the involvement of the AChE peripheral site.

Conclusions:

• AChE plays a crucial role in triggering the fibrillization of PrP82-146, thereby promoting amyloidogenesis.
• The findings highlight the involvement of the AChE peripheral site in this process.
• Compounds targeting the peripheral site of AChE may represent a novel therapeutic strategy for GSS and related amyloid diseases.