Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases  

作　　者：Chenjun Hu Yiqun Yan Yanhong Jin Jun Yang Yongmei Xi Zhen Zhong 

机构地区：[1]Department of Neurology of the Second Afliated Hospital and Department of Human Anatomy,Histology and Embryology,Zhejiang University School of Medicine,Hangzhou 310058,China [2]Department of Physiology and Department of Cardiology of the Second Afliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China [3]Division of Human Reproduction and Developmental Genetics,Women’s Hospital and Institute of Genetics,Zhejiang University School of Medicine,Hangzhou 310006,China

出　　处：《Neuroscience Bulletin》2024年第2期241-254,共14页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82071424);the Zhejiang University Education Foundation Global Partnership Fund(188170+194452115/011).

摘　　要：The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral Sclerosis.In a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into fibrils.Cellular and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent years.This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and secretion.Debates on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also discussed.Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关 键 词：Neurodegenerative diseases Prion-like propagation SEEDING ENDOCYTOSIS Endolyosomal leaking Degradation 

分 类 号：R741[医药卫生—神经病学与精神病学]