Controversies and insights into PTBP1-related astrocyte-neuron transdifferentiation:neuronal regeneration strategies for Parkinson’s and Alzheimer’s disease  

作　　者：Simon McDowall Vaishali Bagda Stuart Hodgetts Frank Mastaglia Dunhui Li 

机构地区：[1]Perron Institute for Neurological and Translational Science,Nedlands,WA,Australia [2]School of Human Sciences,The University of Western Australia,Crawley,Perth,WA,Australia [3]Department of Anatomy and Department of Pathology,University of California San Francisco,San Francisco,CA,USA [4]Centre for Molecular Medicine and Innovative Therapeutics,Health Futures Institute,Murdoch University,Murdoch,WA,Australia [5]Centre for Neuromuscular and Neurological Disorders,Nedlands,WA,Australia [6]Department of Neurology and Stephen and Denise Adams Center for Parkinson’s Disease Research,Yale School of Medicine,New Haven,CT,USA

出　　处：《Translational Neurodegeneration》2024年第1期184-199,共16页转化神经变性病(英文)

基　　金：funded by Bryant Stokes Neurological Research Fund,FightMND Drug Development Grant,and Channel 7 Telethon research grant.

摘　　要：Promising therapeutic strategies are being explored to replace or regenerate the neuronal populations that are lost in patients with neurodegenerative disorders.Several research groups have attempted direct reprogramming of astrocytes into neurons by manipulating the expression of polypyrimidine tract-binding protein 1(PTBP1)and claimed putative converted neurons to be functional,which led to improved disease outcomes in animal models of several neurodegenerative disorders.However,a few other studies reported data that contradict these claims,raising doubt about whether PTBP1 suppression truly reprograms astrocytes into neurons and the therapeutic potential of this approach.This review discusses recent advances in regenerative therapeutics including stem cell transplantations for central nervous system disorders,with a particular focus on Parkinson’s and Alzheimer’s diseases.We also provide a perspective on this controversy by considering that astrocyte heterogeneity may be the key to understanding the discrepancy in published studies,and that certain subpopulations of these glial cells may be more readily converted into neurons.

关 键 词：Neuronal regeneration Astrocyte-neuron reprogramming Astrocyte heterogeneity Therapeutic strategies 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R749.16[医药卫生—临床医学]