Therapeutic targeting of cellular prion protein:toward the development of dual mechanism anti-prion compounds
Antonio Masone1
Chiara Zucchelli2
Enrico Caruso3
Giovanna Musco2
Roberto Chiesa1
1.Laboratory of Prion Neurobiology,Department of Neuroscience,Istituto di Ricerche Farmacologiche Mario Negri IRCCS,Milan,Italy2.Biomolecular NMR Unit,Division of Genetics and Cell Biology,IRCCS Ospedale San Raffaele,Milan,Italy3.Department of Biotechnology and Life Sciences,University of Insubria,Varese,Italy
摘要：PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPc),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSc can adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPc is the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target for prion diseases.In this minireview,we briefly outline the approaches to target PrPc and discuss our recent identification of Zn(Ⅱ)-BnPyP,a PrPc-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-BnPyP targets PrPc may lead toward the development of a new class of dual mechanism anti-prion compounds.
机标关键词：developmentmechanismcellularproteindualanti-prioncompoundstargeting
论文发表日期：2025-04-27
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：6( 1009-1014 )
英文信息