Decrease of Protease-Resistant PrP^Sc Level in ScN2a Cells by Polyornithine and Polyhistidine.

Area of Science:

• Neuroscience
• Biochemistry
• Cell Biology

Background:

• Previous research indicated poly-L-lysine and poly-L-arginine possess anti-prion properties.
• Prion diseases are fatal neurodegenerative disorders characterized by the misfolding of the prion protein (PrP).

Purpose of the Study:

• To evaluate the anti-prion efficacy of various poly-amino acids, including poly-L-ornithine (PLO), poly-L-histidine (PLH), poly-L-glutamic acid (PLE), and poly-L-threonine (PLT).
• To investigate the correlation between poly-amino acid properties and their ability to inhibit prion propagation in cultured cells.

Main Methods:

• Utilized chronically prion-infected ScN2a cells to assess anti-prion activity.
• Quantified the levels of PrPSc in cells treated with different poly-amino acids.

Main Results:

• Poly-L-ornithine (PLO) and poly-L-histidine (PLH) demonstrated significant inhibition of PrPSc levels.
• Anionic poly-L-glutamic acid (PLE) and uncharged poly-L-threonine (PLT) did not affect PrPSc levels.
• The anti-prion efficacy of poly-basic amino acids correlated with their cationicity.

Conclusions:

• Cationic poly-basic amino acids, specifically PLO and PLH, exhibit potent anti-prion activity.
• The anti-prion activity of these compounds is linked to their functional group cationicity and interaction with acidic cellular compartments.