Astrocyte in prion disease: a double-edged sword  

作　　者：Waqas Tahir Simrika Thapa Hermann M.Schatzl 

机构地区：[1]Department of Comparative Biology&Experimental Medicine,Faculty of Veterinary Medicine,University of Calgary,Calgary,AB,Canada [2]Calgary Prion Research Unit,University of Calgary,Calgary,AB,Canada [3]Hotchkiss Brain Institute,University of Calgary,Calgary,AB,Canada

出　　处：《Neural Regeneration Research》2022年第8期1659-1665,共7页中国神经再生研究（英文版）

基　　金：supported by grants from Alberta Innovates/Alberta Prion Research Institute(APRI grants 201600010 and 201900008)(to HMS);ST had received a University of Calgary Eyes High,Killam and Alberta Innovates Health Solution(AIHS)doctoral fellowship.

摘　　要：Prion diseases are infectious protein misfolding disorders of the central nervous system that result from misfolding of the cellular prion protein(PrPC)into the pathologic isoform PrPSc.Pathologic hallmarks of prion disease are depositions of pathological prion protein PrPSc,neuronal loss,spongiform degeneration and astrogliosis in the brain.Prion diseases affect human and animals,there is no effective therapy,and they invariably remain fatal.For a long time,neuronal loss was considered the sole reason for neurodegeneration in prion pathogenesis,and the contribution of non-neuronal cells like microglia and astrocytes was considered less important.Recent evidence suggests that neurodegeneration during prion pathogenesis is a consequence of a complex interplay between neuronal and non-neuronal cells in the brain,but the exact role of these non-neuronal cells during prion pathology is still elusive.Astrocytes are non-neuronal cells that regulate brain homeostasis under physiological conditions.However,astrocytes can deposit PrPSc aggregates and propagate prions in prion-infected brains.Additionally,sub-populations of reactive astrocytes that include neurotrophic and neurotoxic species have been identified,differentially expressed in the brain during prion infection.Revealing the exact role of astrocytes in prion disease is hampered by the lack of in vitro models of prion-infected astrocytes.Recently,we established a murine astrocyte cell line persistently infected with mouse-adapted prions,and showed how such astrocytes differentially process various prion strains.Considering the complexity of the role of astrocytes in prion pathogenesis,we need more in vitro and in vivo models for exploring the contribution of sub-populations of reactive astrocytes,their differential regulation of signaling cascades,and the interaction with neurons and microglia during prion pathogenesis.This will help to establish novel in vivo models and define new therapeutic targets against prion diseases.In this review,we will discuss the comp

关 键 词：Alzheimer’s disease ASTROCYTES central nervous system Creutzfeldt-Jakob disease glial cells NEURODEGENERATION PRION prion disease prion protein SCRAPIE 

分 类 号：R742.9[医药卫生—神经病学与精神病学]