[Therapeutics for prion diseases].
Recent outbreaks of acquired forms of human prion diseases in younger people are promoting the development of prophylaxis and therapeutics. One possible target for therapeutic interventions is to inhibit the biosynthesis and accumulation of an abnormal isoform of prion protein, which is supposed to be a pathogen itself. Here, our current in-vitro and in-vivo data on anti-prion chemicals with amyloid binding capacity, represented by pentosan polysulfate and thioflavin-related chemicals, are presented, and structural aspects on the interaction between prion protein molecules and anti-prion chemicals including quinacrine are discussed. The current status of clinical trials using quinacrine or pentosan polysulfate is also reviewed. Finally, key structure(s) in the prion protein molecules, important to inhibit the conversion into abnormal prion protein molecules, are discussed in terms of pharmacology, and possibility of the in-silico rational drug design is also referred. Exploitation of anti-prion drugs should facilitate to solve the enigma of "prion" which can be the only creature against the central dogma, in addition to its contributing to the people with the illness or the people in high risks.
Doh-ura
Katsumi
K
Department of Prion Research, Tohoku University.
D000682:Amyloid / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology / Q000627:therapeutic use*; D017096:Prion Diseases / Q000188:drug therapy*; D011328:Prions / Q000378:metabolism; D011485:Protein Binding; D011796:Quinacrine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use
D000682:Amyloid; D052160:Benzothiazoles; D011328:Prions; D013844:Thiazoles; C009462:thioflavin T; D010426:Pentosan Sulfuric Polyester; D011796:Quinacrine