Inducing prion protein shedding as a neuroprotective and regenerative approach in pathological conditions of the brain:from theory to facts  

作　　者：Andreu Matamoros-Angles Behnam Mohammadi Feizhi Song Mohsin Shafiq Santra Brenna Berta Puig Markus Glatzel Hermann C.Altmeppen 

机构地区：[1]Institute of Neuropathology,University Medical Center Hamburg-Eppendorf(UKE),Hamburg,Germany [2]Department of Neurology,Experimental Research in Stroke and Inflammation(ERSI),University Medical Center Hamburg-Eppendorf(UKE),Hamburg,Germany

出　　处：《Neural Regeneration Research》2023年第9期1869-1875,共7页中国神经再生研究（英文版）

基　　金：supported by funding from the Creutzfeldt-Jakob Disease Foundation;Inc.(USA);the Alzheimer Forschung Initiative (AFI e.V.,Germany);the Werner-Otto-Stiftung (Hamburg,Germany)(all to HCA);the China Scholarship Council (to FS);European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie Grant Agreement N°101030402 (to AMA);Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Center (CRC) 877"Proteolysis as a regulatory event in pathophysiology"(to MG)。

摘　　要：In the last decades,the role of the prion protein(PrP) in neurodegenerative diseases has been intensively investigated,initially in prion diseases of humans(e.g., Creutzfeldt-J akob disease) and animals(e.g.,scrapie in sheep,chronic wasting disease in deer and elk,or "mad cow disease" in cattle).Templated misfolding of physiological cellular prion protein(PrPC) into an aggregation-prone isoform(termed PrP "Scrapie"(PrPSc)),self-re plication and spreading of the latter inside the brain and to peripheral tissues,and the associated formation of infectious proteopathic seeds(termed "prions")are among the essential pathogenic mechanisms underlying this group of fatal and transmissible spongiform encephalopathies.Late r,key roles of the correctly folded PrPCwere identified in more common human brain diseases(such as Alzheimer s disease or Parkinson’s disease) associated with the misfolding and/or accumulation of other proteins(such as amyloid-β,tau or α-synuclein,respectively).PrPChas also been linked with n euro protective and regenerative functions,for instance in hypoxic/ischemic conditions such as stroke.However,despite a mixed "bouquet" of suggested functions,our understanding of pathological and,especially,physiological roles played by PrPCin the brain and beyond is ce rtainly incomplete.Interactions with various other proteins at the cell surfa ce or within intracellular compartments may account for the functional diversity linked with PrPC.Moreover,conserved endogenous proteolytic processing of PrPCgenerates seve ral defined PrPCfragments,possibly holding intrinsic functions in physiological and pathological conditions,thus making the "true and complete biology" of this protein more complicated to be elucidated.Here,we focus on one of those released PrPCfragments,namely shed PrP(sPrP),generated by a membrane-proximate ADAM10-mediated cleavage event at the cell surfa ce.Similar to other soluble PrP fragments(such as the N1 fragment representing PrP’s released N-terminal tail upon the major α-cleavage even

关 键 词：ADAM10 aggregation Alzheimer’s disease AMYLOID antibodies Creutzfeldt-Jakob disease enzymatic cleavage extracellular vesicles NEURODEGENERATION NEUROTOXICITY proteolytic processing stroke transmissible spongiform encephalopathies 

分 类 号：R741.02[医药卫生—神经病学与精神病学]