Anti-prion activity of protein-bound polysaccharide K in prion-infected cells and animals

• Published in: Biochemical and biophysical research communications 2011-02, Vol.405 (2), p.285-290
• Main Authors: Hamanaka, Taichi, Sakasegawa, Yuji, Ohmoto, Akihiro, Kimura, Tomohiro, Ando, Takao, Doh-ura, Katsumi
• Format: Article
• Language: English
• Subjects: Animals; Autophagy; Cell Line, Tumor; Fungal Proteins - chemistry; Fungal Proteins - pharmacology; Fungal Proteins - therapeutic use; Immunotherapeutic agent; Immunotherapy; Mice; Mice, Inbred Strains; Polysaccharides - chemistry; Polysaccharides - pharmacology; Polysaccharides - therapeutic use; Prion; Prion Diseases - drug therapy; Prion-infected cells; Protein-bound polysaccharide K; PrPC Proteins - antagonists & inhibitors; PrPC Proteins - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.01.030

► Our findings provide the first evidence of protein-bound polysaccharide K (PSK) as a new type of anti-prion compound. ► K PSK has anti-prion activity in vitro and in vivo. ► High molecular weight protein component(s) of PSK mainly cause anti-prion activity. ► PSK may be useful in elucidating the mechanism of prion replication. Protein-bound polysaccharide K (PSK) is a clinical immunotherapeutic agent that exhibits various biological activities, including anti-tumor and anti-microbial effects. In the present study, we report on the anti-prion activity of PSK. It inhibited the formation of protease-resistant abnormal prion protein in prion-infected cells without any apparent alterations in either the normal prion protein turnover or the autophagic function in the cells. Its anti-prion activity was predominantly composed of the high molecular weight component(s) of the protein portion of PSK. A single subcutaneous dose of PSK slightly but significantly prolonged the survival time of peritoneally prion-infected mice, but PSK-treated mice produced neutralizing antibodies against the anti-prion activity of PSK. These findings suggest that PSK is a new anti-prion substance that may be useful in elucidating the mechanism of prion replication, although the structure of the anti-prion component(s) of PSK requires further evaluation.