Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds  

作　　者：Antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa 

机构地区：[1]Laboratory of Prion Neurobiology,Department of Neuroscience,Istituto di Ricerche Farmacologiche Mario Negri IRCCS,Milan,Italy [2]Biomolecular NMR Unit,Division of Genetics and Cell Biology,IRCCS Ospedale San Raffaele,Milan,Italy [3]Department of Biotechnology and Life Sciences,University of Insubria,Varese,Italy

出　　处：《Neural Regeneration Research》2025年第4期1009-1014,共6页中国神经再生研究（英文版）

基　　金：supported by Telethon Italy award GGP15225(to RC and GM);Italian Ministry of Health award RF-2016-02362950(to RC and CZ);the CJD Foundation USA(to RC);the Associazione Italiana Encefalopatie da Prioni(AIEnP)(to RC).

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.PrPSccan 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 PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,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)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关 键 词：anti-prion drug anti-PrPC antibody antisense oligonucleotide NEURODEGENERATION pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor 

分 类 号：R96[医药卫生—药理学]