Complex Polyamines: Unique Prion Disaggregating Compounds

Title: Complex Polyamines: Unique Prion Disaggregating Compounds

Volume: 8 Issue: 5

Author(s): Surachai Supattapone, Justin R. Piro and Judy R. Rees

Affiliation:

Keywords: Prion, PrPSc, branched polyamines, dendrimers

Abstract: Among the candidate anti-prion chemotherapeutic agents identified to date, complex polyamines constitute the only class of compounds that possess the ability to remove pre-existing PrPSc molecules from infected cells. The potency of branched polyamines such as cationic dendrimers increases with the density of positive charges on their surface. Cationic dendrimers appear to accumulate together with PrPSc molecules in lysosomes, where the acidic environment facilitates dendrimer-mediated PrPSc disaggregation. Dendrimers can disaggregate a range of different amyloid proteins by interacting with specific epitopes on each protein. Studies with model peptides suggest that dendrimers may cause fiber breakage and capping of elongating fibers. Potential limitations to the development of dendrimers as therapeutic compounds for neurodegenerative disorders of protein misfolding such as prion diseases include poor bioavailability, limited spectrum of activity, and detrimental neurological side effects. A related group of compounds, lipopolyamines, are smaller molecules containing a lipophilic tail that may assist membrane targeting. Developing strategies to enable the safe delivery of potent complex polyamines to the central nervous system represents a critical avenue for future research.

Cite this article as:

Supattapone Surachai, Piro R. Justin and Rees R. Judy, Complex Polyamines: Unique Prion Disaggregating Compounds, CNS & Neurological Disorders - Drug Targets 2009; 8 (5) . https://dx.doi.org/10.2174/187152709789541952