Potential of astrocytes in targeting therapy for Alzheimer?s disease

被引:6
作者
Bi, Wangyu [1 ]
Lei, Tong [1 ]
Cai, Shanglin [1 ]
Zhang, Xiaoshuang [1 ]
Yang, Yanjie [1 ]
Xiao, Zhuangzhuang [1 ]
Wang, Lei [1 ,2 ]
Du, Hongwu [1 ,2 ]
机构
[1] Univ Sci & Technol Beijing, Sch Chem & Biol Engn, Beijing 100083, Peoples R China
[2] Univ Sci & Technol Beijing, Daxing Res Inst, Beijing, Peoples R China
关键词
Alzheimer?s disease; Hyperphosphorylated tau; Astrocyte; Neuroinflammation; -Amyloid plaques; MESENCHYMAL STEM-CELLS; SYNAPTIC DYSFUNCTION; NEURONAL-ACTIVITY; OXIDATIVE STRESS; AMYLOID PLAQUES; TAU PATHOLOGY; MOUSE MODEL; DIFFERENTIATION; CHOLESTEROL; ACTIVATION;
D O I
10.1016/j.intimp.2022.109368
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
As the most common neurodegenerative disease, Alzheimer's disease (AD) exhibits an incomprehensible path-ogenesis, which has led to the continuous failure of drug development in recent years. Although neuronal damage is considered a pathological feature of AD, treatment strategies targeting beta-amyloid (A beta) have not achieved beneficial effects. In-depth research on glial cells has revealed the strong importance and application prospects of astrocytes in the recovery of cognitive functions. This review summarizes the role of astrocytes in AD and the possibility of therapeutic strategies targeting astrocytes. Astrocytes are involved in brain lipid meta-bolism and can regulate the synthesis and degradation of A beta to affect the pathology of AD. The tau protein is phosphorylated by astrocytes, and this phosphorylation leads to the formation of neurofibrillary tangles (NFTs). Astrocytes can express a variety of receptors and inflammatory factors and participate in the neuroinflammatory process and the release of proinflammatory mediators. When the glutamate produced by the neurons is not cleared by astrocytes, neurons undergo apoptosis due to blocked cell metabolism. Therapies for astrocytes are highly efficient, and these include stem cell therapy, gene editing technology, astrocyte transformation and chemical drugs. Here, we discuss the advantages and disadvantages of animal and cell models applied to the study of targeted astrocyte therapies. This study helps elucidate the mechanism of astrocytes in AD and promotes the clinical application of potential therapeutic strategies targeting astrocytes.
引用
收藏
页数:14
相关论文
共 173 条
[1]   Astrocyte Dysfunction in Alzheimer Disease [J].
Acosta, Crystal ;
Anderson, Hope D. ;
Anderson, Christopher M. .
JOURNAL OF NEUROSCIENCE RESEARCH, 2017, 95 (12) :2430-2447
[2]   Prospect of mesenchymal stem cells in therapy of osteoporosis: A review [J].
Aghebati-Maleki, Leili ;
Dolati, Sanam ;
Zandi, Reza ;
Fotouhi, Ali ;
Ahmadi, Majid ;
Aghebati, Ali ;
Nouri, Mohammad ;
Shakouri, Seyed Kazem ;
Yousefi, Mehdi .
JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (06) :8570-8578
[3]   Glial Cell: A Potential Target for Cellular and Drug Based Therapy in Various CNS Diseases [J].
Ahmed, Shakeeb ;
Gull, Azka ;
Khuroo, Tahir ;
Aqil, Mohd. ;
Sultana, Yasmin .
CURRENT PHARMACEUTICAL DESIGN, 2017, 23 (16) :2389-2399
[4]   Targeting innate immunity for neurodegenerative disorders of the central nervous system [J].
Andreasson, Katrin I. ;
Bachstetter, Adam D. ;
Colonna, Marco ;
Ginhoux, Florent ;
Holmes, Clive ;
Lamb, Bruce ;
Landreth, Gary ;
Lee, Daniel C. ;
Low, Donovan ;
Lynch, Marina A. ;
Monsonego, Alon ;
O'Banion, M. Kerry ;
Pekny, Milos ;
Puschmann, Till ;
Russek-Blum, Niva ;
Sandusky, Leslie A. ;
Selenica, Maj-Linda B. ;
Takata, Kazuyuki ;
Teeling, Jessica ;
Town, Terrence ;
Van Eldik, Linda J. .
JOURNAL OF NEUROCHEMISTRY, 2016, 138 (05) :653-693
[5]   Interpretation of risk loci from genome-wide association studies of Alzheimer's disease [J].
Andrews, Shea J. ;
Fulton-Howard, Brian ;
Goate, Alison .
LANCET NEUROLOGY, 2020, 19 (04) :326-335
[6]   Targeting Neuroinflammation to Treat Alzheimer's Disease [J].
Ardura-Fabregat, A. ;
Boddeke, E. W. G. M. ;
Boza-Serrano, A. ;
Brioschi, S. ;
Castro-Gomez, S. ;
Ceyzeriat, K. ;
Dansokho, C. ;
Dierkes, T. ;
Gelders, G. ;
Heneka, Michael T. ;
Hoeijmakers, L. ;
Hoffmann, A. ;
Iaccarino, L. ;
Jahnert, S. ;
Kuhbandner, K. ;
Landreth, G. ;
Lonnemann, N. ;
Loeschmann, P. A. ;
McManus, R. M. ;
Paulus, A. ;
Reemst, K. ;
Sanchez-Caro, J. M. ;
Tiberi, A. ;
Van der Perren, A. ;
Vautheny, A. ;
Venegas, C. ;
Webers, A. ;
Weydt, P. ;
Wijasa, T. S. ;
Xiang, X. ;
Yang, Y. .
CNS DRUGS, 2017, 31 (12) :1057-1082
[7]   Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases [J].
Armada-Moreira, Adam ;
Gomes, Joana, I ;
Pina, Carolina Campos ;
Savchak, Oksana K. ;
Goncalves-Ribeiro, Joana ;
Rei, Nadia ;
Pinto, Sara ;
Morais, Tatiana P. ;
Martins, Robertta Silva ;
Ribeiro, Filipa F. ;
Sebastiao, Ana M. ;
Crunelli, Vincenzo ;
Vaz, Sandra H. .
FRONTIERS IN CELLULAR NEUROSCIENCE, 2020, 14
[8]   Calcium-sensing receptor antagonist (calcilytic) NPS 2143 specifically blocks the increased secretion of endogenous Aβ42 prompted by exogenous fibrillary or soluble Aβ25-35 in human cortical astrocytes and neurons-Therapeutic relevance to Alzheimer's disease [J].
Armato, Ubaldo ;
Chiarini, Anna ;
Chakravarthy, Balu ;
Chioffi, Franco ;
Pacchiana, Raffaella ;
Colarusso, Enzo ;
Whitfield, James F. ;
Dal Pra, Ilaria .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2013, 1832 (10) :1634-1652
[9]   The role of astroglia in Alzheimer's disease: pathophysiology and clinical implications [J].
Arranz, Amaia M. ;
De Strooper, Bart .
LANCET NEUROLOGY, 2019, 18 (04) :406-414
[10]   CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes [J].
Barbar, Lilianne ;
Jain, Tanya ;
Zimmer, Matthew ;
Kruglikov, Ilya ;
Sadick, Jessica S. ;
Wang, Minghui ;
Kalpana, Kriti ;
Rose, Indigo V. L. ;
Burstein, Suzanne R. ;
Rusielewicz, Tomasz ;
Nijsure, Madhura ;
Guttenplan, Kevin A. ;
di Domenico, Angelique ;
Croft, Gist ;
Zhang, Bin ;
Nobuta, Hiroko ;
Hebert, Jean M. ;
Liddelow, Shane A. ;
Fossati, Valentina .
NEURON, 2020, 107 (03) :436-+