Complement System in Alzheimer's Disease

被引:38
作者
Shah, Akash [1 ]
Kishore, Uday [2 ]
Shastri, Abhishek [3 ]
机构
[1] Queen Mary Univ London, Barts & London Sch Med & Dent, London E1 2AD, England
[2] Brunel Univ London, Coll Hlth Med & Life Sci, Biosci, Uxbridge UB8 3PH, Middx, England
[3] Cent & North West London NHS Fdn Trust, London NW1 3AX, England
关键词
neuroinflammation; Alzheimer's disease; complement system; microglia; AMYLOID-BETA-PROTEIN; NECROSIS-FACTOR-ALPHA; MOUSE MODEL; INFLAMMATORY RESPONSE; ALTERNATIVE PATHWAY; DEMENTIA PREVENTION; CLASSICAL PATHWAY; OXIDATIVE STRESS; TRANSGENIC MICE; C-3; CONVERTASE;
D O I
10.3390/ijms222413647
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alzheimer's disease is a type of dementia characterized by problems with short-term memory, cognition, and difficulties with activities of daily living. It is a progressive, neurodegenerative disorder. The complement system is an ancient part of the innate immune system and comprises of more than thirty serum and membrane-bound proteins. This system has three different activating pathways and culminates into the formation of a membrane attack complex that ultimately causes target cell lysis (usually pathogens) The complement system is involved in several important functions in the central nervous system (CNS) that include neurogenesis, synaptic pruning, apoptosis, and neuronal plasticity. Here, we discuss how the complement system is involved in the effective functioning of CNS, while also contributing to chronic neuroinflammation leading to neurodegenerative disorders such as Alzheimer's disease. We also discuss potential targets in the complement system for stopping its harmful effects via neuroinflammation and provide perspective for the direction of future research in this field.
引用
收藏
页数:21
相关论文
共 141 条
[1]   On the path to 2025: understanding the Alzheimer's disease continuum [J].
Aisen, Paul S. ;
Cummings, Jeffrey ;
Jack, Clifford R., Jr. ;
Morris, John C. ;
Sperling, Reisa ;
Froelich, Lutz ;
Jones, Roy W. ;
Dowsett, Sherie A. ;
Matthews, Brandy R. ;
Raskin, Joel ;
Scheltens, Philip ;
Dubois, Bruno .
ALZHEIMERS RESEARCH & THERAPY, 2017, 9
[2]   Activated microglia desialylate their surface, stimulating complement receptor 3-mediated phagocytosis of neurons [J].
Allendorf, David H. ;
Puigdellivol, Mar ;
Brown, Guy C. .
GLIA, 2020, 68 (05) :989-998
[3]   Toll-like receptor 4-dependent glial cell activation mediates the impairment in memory establishment induced by β-amyloid oligomers in an acute mouse model of Alzheimer's disease [J].
Balducci, Claudia ;
Frasca, Angelisa ;
Zotti, Margherita ;
La Vitola, Pietro ;
Mhillaj, Emanuela ;
Grigoli, Emanuele ;
Iacobellis, Martina ;
Grandi, Federica ;
Messa, Massimo ;
Colombo, Laura ;
Molteni, Monica ;
Trabace, Luigia ;
Rossetti, Carlo ;
Salmona, Mario ;
Forloni, Gianluigi .
BRAIN BEHAVIOR AND IMMUNITY, 2017, 60 :188-197
[4]   LAMINA-SPECIFIC ARRANGEMENT OF ASTROCYTIC GLIOSIS AND SENILE PLAQUES IN ALZHEIMERS-DISEASE VISUAL-CORTEX [J].
BEACH, TG ;
MCGEER, EG .
BRAIN RESEARCH, 1988, 463 (02) :357-361
[5]   Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum [J].
Benard, Magalie ;
Raoult, Emilie ;
Vaudry, David ;
Leprince, Jerome ;
Failluel-Morel, Anthony ;
Gonzalez, Bruno J. ;
Galas, Ludovic ;
Vaudry, Hubert ;
Fontaine, Marc .
MOLECULAR IMMUNOLOGY, 2008, 45 (14) :3767-3774
[6]   Reduced removal of synaptic terminals from axotomized spinal motoneurons in the absence of complement C3 [J].
Berg, Alexander ;
Zelano, Johan ;
Stephan, Alexander ;
Thams, Sebastian ;
Barres, Ben A. ;
Pekny, Milos ;
Pekna, Marcela ;
Cullheim, Staffan .
EXPERIMENTAL NEUROLOGY, 2012, 237 (01) :8-17
[7]   Activation of mGluR1 Mediates C1q-Dependent Microglial Phagocytosis of Glutamatergic Synapses in Alzheimer's Rodent Models [J].
Bie, Bihua ;
Wu, Jiang ;
Foss, Joseph F. ;
Naguib, Mohamed .
MOLECULAR NEUROBIOLOGY, 2019, 56 (08) :5568-5585
[8]   Review: Activation patterns of microglia and their identification in the human brain [J].
Boche, D. ;
Perry, V. H. ;
Nicoll, J. A. R. .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2013, 39 (01) :3-18
[9]   Role of complement in neurodegeneration and neuroinflammation [J].
Bonifati, Domenico Marco ;
Kishore, Uday .
MOLECULAR IMMUNOLOGY, 2007, 44 (05) :999-1010
[10]   Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies [J].
Botto, M ;
Dell'Agnola, C ;
Bygrave, AE ;
Thompson, EM ;
Cook, HT ;
Petry, F ;
Loos, M ;
Pandolfi, PP ;
Walport, MJ .
NATURE GENETICS, 1998, 19 (01) :56-59