Login Register Cart 0
Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

cGAS-STING-mediated IFN-I Response in Host Defense and Neuroinflammatory Diseases

Author(s): Kai Chen, Chuan Lai, Ying Su, Wen Dai Bao, Liu Nan Yang, Ping-Ping Xu* and Ling-Qiang Zhu*

Volume 20, Issue 2, 2022

Published on: 07 February, 2022

Page: [362 - 371] Pages: 10

DOI: 10.2174/1570159X19666210924110144

Price: $65

Abstract

The presence of foreign or misplaced nucleic acids is a dangerous signal that triggers innate immune responses by activating cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and binding to its downstream signaling effector stimulator of interferon genes (STING). Then the cGAS-STING pathway activation links nucleic acid-sensing to immune responses and pathogenic entities clearance. However, the overactivation of this signaling pathway leads to fatal immune disorders and contributes to the progression of many human inflammatory diseases. Therefore, optimal activation of this pathway is crucial for the elimination of invading pathogens and the maintenance of immune homeostasis. In this review, we will summarize its fundamental roles in initiating host defense against invading pathogens and discuss its pathogenic roles in multiple neuro-inflammatory diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and other neurodegenerative diseases.

Keywords: cGAS, STING, neuroinflammation, AD, PD, HD, ALS, MS.

« Previous Next »
Graphical Abstract

[1]
Wu, J.; Chen, Z.J. Innate immune sensing and signaling of cytosolic nucleic acids. Annu. Rev. Immunol., 2014, 32, 461-488.
[http://dx.doi.org/10.1146/annurev-immunol-032713-120156] [PMID: 24655297]
[2]
Takeuchi, O.; Akira, S. Pattern recognition receptors and inflammation. Cell, 2010, 140(6), 805-820.
[http://dx.doi.org/10.1016/j.cell.2010.01.022] [PMID: 20303872]
[3]
Kato, K.; Omura, H.; Ishitani, R.; Nureki, O. Cyclic GMP-AMP as an endogenous second messenger in innate immune signaling by cytosolic DNA. Annu. Rev. Biochem., 2017, 86(1), 541-566.
[http://dx.doi.org/10.1146/annurev-biochem-061516-044813] [PMID: 28399655]
[4]
Wu, J.; Sun, L.; Chen, X.; Du, F.; Shi, H.; Chen, C.; Chen, Z.J. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science, 2013, 339(6121), 826-830.
[http://dx.doi.org/10.1126/science.1229963] [PMID: 23258412]
[5]
Sun, L.; Wu, J.; Du, F.; Chen, X.; Chen, Z.J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science, 2013, 339(6121), 786-791.
[http://dx.doi.org/10.1126/science.1232458] [PMID: 23258413]
[6]
Burdette, D.L.; Monroe, K.M.; Sotelo-Troha, K.; Iwig, J.S.; Eckert, B.; Hyodo, M.; Hayakawa, Y.; Vance, R.E. STING is a direct innate immune sensor of cyclic di-GMP. Nature, 2011, 478(7370), 515-518.
[http://dx.doi.org/10.1038/nature10429] [PMID: 21947006]
[7]
Ishikawa, H.; Barber, G.N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature, 2008, 455(7213), 674-678.
[http://dx.doi.org/10.1038/nature07317] [PMID: 18724357]
[8]
Barbalat, R.; Ewald, S.E.; Mouchess, M.L.; Barton, G.M. Nucleic acid recognition by the innate immune system. Annu. Rev. Immunol., 2011, 29, 185-214.
[http://dx.doi.org/10.1146/annurev-immunol-031210-101340] [PMID: 21219183]
[9]
O’Neill, L.A. Immunology. Sensing the dark side of DNA. Science, 2013, 339(6121), 763-764.
[http://dx.doi.org/10.1126/science.1234724] [PMID: 23413341]
[10]
Choe, C-H.; Park, I.S.; Park, J.; Yu, K-Y.; Jang, H.; Kim, J.; Jang, Y-S. Transmembrane protein 173 inhibits RANKL-induced osteoclast differentiation. FEBS Lett., 2015, 589(7), 836-841.
[http://dx.doi.org/10.1016/j.febslet.2015.02.018] [PMID: 25728277]
[11]
Jin, L.; Waterman, P.M.; Jonscher, K.R.; Short, C.M.; Reisdorph, N.A.; Cambier, J.C. MPYS, a novel membrane tetraspanner, is associated with major histocompatibility complex class II and mediates transduction of apoptotic signals. Mol. Cell. Biol., 2008, 28(16), 5014-5026.
[http://dx.doi.org/10.1128/MCB.00640-08] [PMID: 18559423]
[12]
Zhong, B.; Yang, Y.; Li, S.; Wang, Y-Y.; Li, Y.; Diao, F.; Lei, C.; He, X.; Zhang, L.; Tien, P.; Shu, H.B. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity, 2008, 29(4), 538-550.
[http://dx.doi.org/10.1016/j.immuni.2008.09.003] [PMID: 18818105]
[13]
Sun, W.; Li, Y.; Chen, L.; Chen, H.; You, F.; Zhou, X.; Zhou, Y.; Zhai, Z.; Chen, D.; Jiang, Z. ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization. Proc. Natl. Acad. Sci. USA, 2009, 106(21), 8653-8658.
[http://dx.doi.org/10.1073/pnas.0900850106] [PMID: 19433799]
[14]
Chen, Q.; Sun, L.; Chen, Z.J. Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat. Immunol., 2016, 17(10), 1142-1149.
[http://dx.doi.org/10.1038/ni.3558] [PMID: 27648547]
[15]
Motwani, M.; Pesiridis, S.; Fitzgerald, K.A. DNA sensing by the cGAS-STING pathway in health and disease. Nat. Rev. Genet., 2019, 20(11), 657-674.
[http://dx.doi.org/10.1038/s41576-019-0151-1] [PMID: 31358977]
[16]
Liu, S.; Cai, X.; Wu, J.; Cong, Q.; Chen, X.; Li, T.; Du, F.; Ren, J.; Wu, Y.T.; Grishin, N.V. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science 2015, 347(6227), aaa2630-aaa2630-14.
[17]
Kawai, T.; Akira, S. Innate immune recognition of viral infection. Nat. Immunol., 2006, 7(2), 131-137.
[http://dx.doi.org/10.1038/ni1303] [PMID: 16424890]
[18]
de Weerd, N.A.; Samarajiwa, S.A.; Hertzog, P.J.; Type, I. Type I interferon receptors: biochemistry and biological functions. J. Biol. Chem., 2007, 282(28), 20053-20057.
[http://dx.doi.org/10.1074/jbc.R700006200] [PMID: 17502368]
[19]
Nandakumar, R.; Tschismarov, R.; Meissner, F.; Prabakaran, T.; Krissanaprasit, A.; Farahani, E.; Zhang, B.C.; Assil, S.; Martin, A.; Bertrams, W.; Holm, C.K.; Ablasser, A.; Klause, T.; Thomsen, M.K.; Schmeck, B.; Howard, K.A.; Henry, T.; Gothelf, K.V.; Decker, T.; Paludan, S.R. Intracellular bacteria engage a STING-TBK1-MVB12b pathway to enable paracrine cGAS-STING signalling. Nat. Microbiol., 2019, 4(4), 701-713.
[http://dx.doi.org/10.1038/s41564-019-0367-z] [PMID: 30804548]
[20]
Li, Q.; Liu, C.; Yue, R.; El-Ashram, S.; Wang, J.; He, X.; Zhao, D.; Zhou, X.; Xu, L. cGAS/STING/TBK1/IRF3 signaling pathway activates BMDCs maturation following mycobacterium bovis infection. Int. J. Mol. Sci., 2019, 20(4), 895.
[http://dx.doi.org/10.3390/ijms20040895] [PMID: 30791397]
[21]
Ruangkiattikul, N.; Nerlich, A.; Abdissa, K.; Lienenklaus, S.; Suwandi, A.; Janze, N.; Laarmann, K.; Spanier, J.; Kalinke, U.; Weiss, S.; Goethe, R. cGAS-STING-TBK1-IRF3/7 induced interferon-β contributes to the clearing of non tuberculous mycobacterial infection in mice. Virulence, 2017, 8(7), 1303-1315.
[http://dx.doi.org/10.1080/21505594.2017.1321191] [PMID: 28422568]
[22]
McGuckin Wuertz, K.; Treuting, P.M.; Hemann, E.A.; Esser-Nobis, K.; Snyder, A.G.; Graham, J.B.; Daniels, B.P.; Wilkins, C.; Snyder, J.M.; Voss, K.M.; Oberst, A.; Lund, J.; Gale, M. Jr STING is required for host defense against neuropathological West Nile virus infection. PLoS Pathog., 2019, 15(8)e1007899
[http://dx.doi.org/10.1371/journal.ppat.1007899] [PMID: 31415679]
[23]
Mathur, V.; Burai, R.; Vest, R.T.; Bonanno, L.N.; Lehallier, B.; Zardeneta, M.E.; Mistry, K.N.; Do, D.; Marsh, S.E.; Abud, E.M.; Blurton-Jones, M.; Li, L.; Lashuel, H.A.; Wyss-Coray, T. Activation of the STING-Dependent Type I interferon response reduces microglial reactivity and neuroinflammation. Neuron, 2017, 96(6), 1290-1302.e6.
[http://dx.doi.org/10.1016/j.neuron.2017.11.032] [PMID: 29268096]
[24]
Jia, M.; Qin, D.; Zhao, C.; Chai, L.; Yu, Z.; Wang, W.; Tong, L.; Lv, L.; Wang, Y.; Rehwinkel, J.; Yu, J.; Zhao, W. Redox homeostasis maintained by GPX4 facilitates STING activation. Nat. Immunol., 2020, 21(7), 727-735.
[http://dx.doi.org/10.1038/s41590-020-0699-0] [PMID: 32541831]
[25]
Minter, M.R.; Moore, Z.; Zhang, M.; Brody, K.M.; Jones, N.C.; Shultz, S.R.; Taylor, J.M.; Crack, P.J. Deletion of the type-1 interferon receptor in APPSWE/PS1ΔE9 mice preserves cognitive function and alters glial phenotype. Acta Neuropathol. Commun., 2016, 4(1), 72-72.
[http://dx.doi.org/10.1186/s40478-016-0341-4] [PMID: 27400725]
[26]
Taylor, J.M.; Minter, M.R.; Newman, A.G.; Zhang, M.; Adlard, P.A.; Crack, P.J. Type-1 interferon signaling mediates neuro-inflammatory events in models of Alzheimer’s disease. Neurobiol. Aging, 2014, 35(5), 1012-1023.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.10.089] [PMID: 24262201]
[27]
Mesquita, S.D.; Ferreira, A.C.; Gao, F.; Coppola, G.; Geschwind, D.H.; Sousa, J.C.; Correia-Neves, M.; Sousa, N.; Palha, J.A.; Marques, F. The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer’s disease. Brain Behav. Immun., 2015, 49, 280-292.
[http://dx.doi.org/10.1016/j.bbi.2015.06.008] [PMID: 26092102]
[28]
Main, B.S.; Zhang, M.; Brody, K.M.; Ayton, S.; Frugier, T.; Steer, D.; Finkelstein, D.; Crack, P.J.; Taylor, J.M. Type-1 interferons contribute to the neuroinflammatory response and disease progression of the MPTP mouse model of Parkinson’s disease. Glia, 2016, 64(9), 1590-1604.
[http://dx.doi.org/10.1002/glia.23028] [PMID: 27404846]
[29]
Sliter, D.A.; Martinez, J.; Hao, L.; Chen, X.; Sun, N.; Fischer, T.D.; Burman, J.L.; Li, Y.; Zhang, Z.; Narendra, D.P.; Cai, H.; Borsche, M.; Klein, C.; Youle, R.J. Parkin and PINK1 mitigate STING-induced inflammation. Nature, 2018, 561(7722), 258-262.
[http://dx.doi.org/10.1038/s41586-018-0448-9] [PMID: 30135585]
[30]
Helbi, S.; Ravanbakhsh, B.; Karimi, M.; Kooti, W.; Jivad, N. Aligned Expression of IFI16 and STING Genes in RRMS Patients’ Blood. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19, 1-9.
[31]
Casella, G.; Rasouli, J.; Mason, K.; Boehm, A.; Kumar, G.; Hwang, D.; Thome, R.; Ishikawa, L.; Zhang, G-X.; Ciric, B.; Rostami, A. A serine protease inhibitor suppresses autoimmune neuroinflammation by activating the STING/IFN-β axis in macrophages. Cell. Mol. Immunol., 2020, 17(12), 1278-1280.
[http://dx.doi.org/10.1038/s41423-020-0405-z] [PMID: 32203194]
[32]
Yu, C.H.; Davidson, S.; Harapas, C.R.; Hilton, J.B.; Mlodzianoski, M.J.; Laohamonthonkul, P.; Louis, C.; Low, R.R.J.; Moecking, J.; De Nardo, D.; Balka, K.R.; Calleja, D.J.; Moghaddas, F.; Ni, E.; McLean, C.A.; Samson, A.L.; Tyebji, S.; Tonkin, C.J.; Bye, C.R.; Turner, B.J.; Pepin, G.; Gantier, M.P.; Rogers, K.L.; McArthur, K.; Crouch, P.J.; Masters, S.L. TDP-43 triggers mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS. Cell, 2020, 183(3), 636-649.e18.
[http://dx.doi.org/10.1016/j.cell.2020.09.020] [PMID: 33031745]
[33]
McCauley, M.E.; O’Rourke, J.G.; Yáñez, A.; Markman, J.L.; Ho, R.; Wang, X.; Chen, S.; Lall, D.; Jin, M.; Muhammad, A.K.M.G.; Bell, S.; Landeros, J.; Valencia, V.; Harms, M.; Arditi, M.; Jefferies, C.; Baloh, R.H. C9orf72 in myeloid cells suppresses STING-induced inflammation. Nature, 2020, 585(7823), 96-101.
[http://dx.doi.org/10.1038/s41586-020-2625-x] [PMID: 32814898]
[34]
Sharma, M.; Rajendrarao, S.; Shahani, N.; Ramírez-Jarquín, U.N.; Subramaniam, S. Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease. Proc. Natl. Acad. Sci. USA, 2020, 117(27), 15989-15999.
[http://dx.doi.org/10.1073/pnas.2002144117] [PMID: 32581130]
[35]
Jauhari, A.; Baranov, S.V.; Suofu, Y.; Kim, J.; Singh, T.; Yablonska, S.; Li, F.; Wang, X.; Oberly, P.; Minnigh, M.B.; Poloyac, S.M.; Carlisle, D.L.; Friedlander, R.M. Melatonin inhibits cytosolic mitochondrial DNA-induced neuroinflammatory signaling in accelerated aging and neurodegeneration. J. Clin. Invest., 2020, 130(6), 3124-3136.
[http://dx.doi.org/10.1172/JCI135026] [PMID: 32182222]
[36]
Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science, 2002, 297(5580), 353-356.
[http://dx.doi.org/10.1126/science.1072994] [PMID: 12130773]
[37]
Jack, C.R.J., Jr; Knopman, D.S.; Jagust, W.J.; Petersen, R.C.; Weiner, M.W.; Aisen, P.S.; Shaw, L.M.; Vemuri, P.; Wiste, H.J.; Weigand, S.D.; Lesnick, T.G.; Pankratz, V.S.; Donohue, M.C.; Trojanowski, J.Q. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol., 2013, 12(2), 207-216.
[http://dx.doi.org/10.1016/S1474-4422(12)70291-0] [PMID: 23332364]
[38]
Park, S.A.; Han, S.M.; Kim, C.E. New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease. Exp. Mol. Med., 2020, 52(4), 556-568.
[http://dx.doi.org/10.1038/s12276-020-0418-9] [PMID: 32284537]
[39]
D’Andrea, M.R.; Cole, G.M.; Ard, M.D. The microglial phagocytic role with specific plaque types in the Alzheimer disease brain. Neurobiol. Aging, 2004, 25(5), 675-683.
[http://dx.doi.org/10.1016/j.neurobiolaging.2003.12.026] [PMID: 15172747]
[40]
Zimmer, E.R.; Leuzy, A.; Benedet, A.L.; Breitner, J.; Gauthier, S.; Rosa-Neto, P. Tracking neuroinflammation in Alzheimer’s disease: the role of positron emission tomography imaging. J. Neuroinflammation, 2014, 11(1), 120-120.
[http://dx.doi.org/10.1186/1742-2094-11-120] [PMID: 25005532]
[41]
Minter, M.R.; Taylor, J.M.; Crack, P.J. The contribution of neuroinflammation to amyloid toxicity in Alzheimer’s disease. J. Neurochem., 2016, 136(3), 457-474.
[http://dx.doi.org/10.1111/jnc.13411] [PMID: 26509334]
[42]
Eikelenboom, P.; van Gool, W.A. Neuroinflammatory perspectives on the two faces of Alzheimer’s disease. J. Neural Transm. (Vienna), 2004, 111(3), 281-294.
[http://dx.doi.org/10.1007/s00702-003-0055-1] [PMID: 14991455]
[43]
Griffin, W.S.T.; Stanley, L.C.; Ling, C.; White, L.; MacLeod, V.; Perrot, L.J.; White, C.L., III; Araoz, C. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc. Natl. Acad. Sci. USA, 1989, 86(19), 7611-7615.
[http://dx.doi.org/10.1073/pnas.86.19.7611] [PMID: 2529544]
[44]
Taylor, J.M.; Moore, Z.; Minter, M.R.; Crack, P.J. Type-I interferon pathway in neuroinflammation and neurodegeneration: focus on Alzheimer’s disease. J. Neural Transm. (Vienna), 2018, 125(5), 797-807.
[http://dx.doi.org/10.1007/s00702-017-1745-4] [PMID: 28676934]
[45]
Baruch, K.; Deczkowska, A.; David, E.; Castellano, J.M.; Miller, O.; Kertser, A.; Berkutzki, T.; Barnett-Itzhaki, Z.; Bezalel, D.; Wyss-Coray, T.; Amit, I.; Schwartz, M. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science, 2014, 346(6205), 89-93.
[http://dx.doi.org/10.1126/science.1252945] [PMID: 25147279]
[46]
Imbimbo, B.P.; Solfrizzi, V.; Panza, F. Are NSAIDs useful to treat Alzheimer’s disease or mild cognitive impairment? Front. Aging Neurosci., 2010, 2, 2.
[http://dx.doi.org/10.3389/fnagi.2010.00019] [PMID: 20725517]
[47]
de Weerd, N.A.; Nguyen, T. The interferons and their receptors--distribution and regulation. Immunol. Cell Biol., 2012, 90(5), 483-491.
[http://dx.doi.org/10.1038/icb.2012.9] [PMID: 22410872]
[48]
Minter, M.R.; Main, B.S.; Brody, K.M.; Zhang, M.; Taylor, J.M.; Crack, P.J. Soluble amyloid triggers a myeloid differentiation factor 88 and interferon regulatory factor 7 dependent neuronal type-1 interferon response in vitro. J. Neuroinflammation, 2015, 12(1), 71-71.
[http://dx.doi.org/10.1186/s12974-015-0263-2] [PMID: 25879763]
[49]
Postuma, R.B.; Berg, D.; Stern, M.; Poewe, W.; Olanow, C.W.; Oertel, W.; Obeso, J.; Marek, K.; Litvan, I.; Lang, A.E.; Halliday, G.; Goetz, C.G.; Gasser, T.; Dubois, B.; Chan, P.; Bloem, B.R.; Adler, C.H.; Deuschl, G. MDS clinical diagnostic criteria for Parkinson’s disease. Mov. Disord., 2015, 30(12), 1591-1601.
[http://dx.doi.org/10.1002/mds.26424] [PMID: 26474316]
[50]
Yao, L.; Ye, Y.; Mao, H.; Lu, F.; He, X.; Lu, G.; Zhang, S. MicroRNA-124 regulates the expression of MEKK3 in the inflammatory pathogenesis of Parkinson’s disease. J. Neuroinflammation, 2018, 15(1), 13-13.
[http://dx.doi.org/10.1186/s12974-018-1053-4] [PMID: 29329581]
[51]
Sun, Q.; Wang, S.; Chen, J.; Cai, H.; Huang, W.; Zhang, Y.; Wang, L.; Xing, Y. MicroRNA-190 alleviates neuronal damage and inhibits neuroinflammation via Nlrp3 in MPTP-induced Parkinson’s disease mouse model. J. Cell. Physiol., 2019, 234(12), 23379-23387.
[http://dx.doi.org/10.1002/jcp.28907] [PMID: 31232472]
[52]
Sampson, T.R.; Debelius, J.W.; Thron, T.; Janssen, S.; Shastri, G.G.; Ilhan, Z.E.; Challis, C.; Schretter, C.E.; Rocha, S.; Gradinaru, V.; Chesselet, M.F.; Keshavarzian, A.; Shannon, K.M.; Krajmalnik-Brown, R.; Wittung-Stafshede, P.; Knight, R.; Mazmanian, S.K. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s Disease. Cell, 2016, 167(6), 1469-1480.e12.
[http://dx.doi.org/10.1016/j.cell.2016.11.018] [PMID: 27912057]
[53]
Gelders, G.; Baekelandt, V.; Der Perren, A.V. Linking neuroinflammation and neurodegeneration in Parkinson’s Disease. Clin. Dev. Immunol., 2018, 20184784268
[http://dx.doi.org/10.1155/2018/4784268]
[54]
Nicoletti, A.; Fagone, P.; Donzuso, G.; Mangano, K.; Dibilio, V.; Caponnetto, S.; Bendtzen, K.; Zappia, M.; Nicoletti, F. Parkinson’s disease is associated with increased serum levels of macrophage migration inhibitory factor. Cytokine, 2011, 55(2), 165-167.
[http://dx.doi.org/10.1016/j.cyto.2011.03.027] [PMID: 21550814]
[55]
Watson, M.B.; Richter, F.; Lee, S.K.; Gabby, L.; Wu, J.; Masliah, E.; Effros, R.B.; Chesselet, M.F. Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein. Exp. Neurol., 2012, 237(2), 318-334.
[http://dx.doi.org/10.1016/j.expneurol.2012.06.025] [PMID: 22750327]
[56]
Gao, D.; Li, T.; Li, X.D.; Chen, X.; Li, Q.Z.; Wight-Carter, M.; Chen, Z.J. Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases. Proc. Natl. Acad. Sci. USA, 2015, 112(42), E5699-E5705.
[http://dx.doi.org/10.1073/pnas.1516465112] [PMID: 26371324]
[57]
Walker, F.O. Huntington’s disease. Lancet, 2007, 369(9557), 218-228.
[http://dx.doi.org/10.1016/S0140-6736(07)60111-1] [PMID: 17240289]
[58]
Bates, G.P.; Dorsey, R.; Gusella, J.F.; Hayden, M.R.; Kay, C.; Leavitt, B.R.; Nance, M.; Ross, C.A.; Scahill, R.I.; Wetzel, R.; Wild, E.J.; Tabrizi, S.J. Huntington disease. Nat. Rev. Dis. Primers, 2015, 1, 15005.
[http://dx.doi.org/10.1038/nrdp.2015.5] [PMID: 27188817]
[59]
Denis, H.L.; Lauruol, F.; Cicchetti, F. Are immunotherapies for Huntington’s disease a realistic option? Mol. Psychiatry, 2019, 24(3), 364-377.
[http://dx.doi.org/10.1038/s41380-018-0021-9] [PMID: 29487401]
[60]
Träger, U.; Andre, R.; Lahiri, N.; Magnusson-Lind, A.; Weiss, A.; Grueninger, S.; McKinnon, C.; Sirinathsinghji, E.; Kahlon, S.; Pfister, E.L.; Moser, R.; Hummerich, H.; Antoniou, M.; Bates, G.P.; Luthi-Carter, R.; Lowdell, M.W.; Björkqvist, M.; Ostroff, G.R.; Aronin, N.; Tabrizi, S.J. HTT-lowering reverses Huntington’s disease immune dysfunction caused by NFκB pathway dysregulation. Brain, 2014, 137(Pt 3), 819-833.
[http://dx.doi.org/10.1093/brain/awt355] [PMID: 24459107]
[61]
Björkqvist, M.; Wild, E.J.; Thiele, J.; Silvestroni, A.; Andre, R.; Lahiri, N.; Raibon, E.; Lee, R.V.; Benn, C.L.; Soulet, D.; Magnusson, A.; Woodman, B.; Landles, C.; Pouladi, M.A.; Hayden, M.R.; Khalili-Shirazi, A.; Lowdell, M.W.; Brundin, P.; Bates, G.P.; Leavitt, B.R.; Möller, T.; Tabrizi, S.J. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington’s disease. J. Exp. Med., 2008, 205(8), 1869-1877.
[http://dx.doi.org/10.1084/jem.20080178] [PMID: 18625748]
[62]
Pavese, N.; Gerhard, A.; Tai, Y.F.; Ho, A.K.; Turkheimer, F.; Barker, R.A.; Brooks, D.J.; Piccini, P. Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology, 2006, 66(11), 1638-1643.
[http://dx.doi.org/10.1212/01.wnl.0000222734.56412.17] [PMID: 16769933]
[63]
Politis, M.; Pavese, N.; Tai, Y.F.; Kiferle, L.; Mason, S.L.; Brooks, D.J.; Tabrizi, S.J.; Barker, R.A.; Piccini, P. Microglial activation in regions related to cognitive function predicts disease onset in Huntington’s disease: a multimodal imaging study. Hum. Brain Mapp., 2011, 32(2), 258-270.
[http://dx.doi.org/10.1002/hbm.21008] [PMID: 21229614]
[64]
Miller, J.R.; Lo, K.K.; Andre, R.; Hensman Moss, D.J.; Träger, U.; Stone, T.C.; Jones, L.; Holmans, P.; Plagnol, V.; Tabrizi, S.J. RNA-Seq of Huntington’s disease patient myeloid cells reveals innate transcriptional dysregulation associated with proinflammatory pathway activation. Hum. Mol. Genet., 2016, 25(14), 2893-2904.
[http://dx.doi.org/10.1093/hmg/ddw142] [PMID: 27170315]
[65]
Labadorf, A.; Hoss, A.G.; Lagomarsino, V.; Latourelle, J.C.; Hadzi, T.C.; Bregu, J.; MacDonald, M.E.; Gusella, J.F.; Chen, J.F.; Akbarian, S.; Weng, Z.; Myers, R.H. RNA Sequence analysis of human huntington disease brain reveals an extensive increase in inflammatory and developmental gene expression. PLoS One, 2015, 10(12)e0143563
[http://dx.doi.org/10.1371/journal.pone.0143563] [PMID: 26636579]
[66]
Genetic Modifiers of Huntington’s Disease (GeM-HD) Consortium. CAG Repeat Not Polyglutamine Length Determines Timing of Huntington’s Disease Onset. Cell, 2019, 178(4), 887-900.e814.
[http://dx.doi.org/10.1016/j.cell.2019.06.036] [PMID: 31398342]
[67]
Hardiman, O.; Al-Chalabi, A.; Chio, A.; Corr, E.M.; Logroscino, G.; Robberecht, W.; Shaw, P.J.; Simmons, Z.; van den Berg, L.H. Amyotrophic lateral sclerosis. Nat. Rev. Dis. Primers, 2017, 3, 17071.
[http://dx.doi.org/10.1038/nrdp.2017.71] [PMID: 28980624]
[68]
Zhao, W.; Beers, D.R.; Bell, S.; Wang, J.; Wen, S.; Baloh, R.H.; Appel, S.H. TDP-43 activates microglia through NF-κB and NLRP3 inflammasome. Exp. Neurol., 2015, 273, 24-35.
[http://dx.doi.org/10.1016/j.expneurol.2015.07.019] [PMID: 26222336]
[69]
Swarup, V.; Phaneuf, D.; Dupré, N.; Petri, S.; Strong, M.; Kriz, J.; Julien, J.P. Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB-mediated pathogenic pathways. J. Exp. Med., 2011, 208(12), 2429-2447.
[http://dx.doi.org/10.1084/jem.20111313] [PMID: 22084410]
[70]
Wang, R.; Yang, B.; Zhang, D. Activation of interferon signaling pathways in spinal cord astrocytes from an ALS mouse model. Glia, 2011, 59(6), 946-958.
[http://dx.doi.org/10.1002/glia.21167] [PMID: 21446050]
[71]
Lu, C.; Allen, K.; Oei, F.; Leoni, E.; Kuhle, J.; Tree, T.; Fratta, P.; Sharma, N.; Sidle, K.; Howard, R.; Orrell, R.; Fish, M.; Greensmith, L.; Pearce, N.; Gallo, V.; Malaspina, A. Systemic inflammatory response and neuromuscular involvement in amyotrophic lateral sclerosis. Neurol. Neuroimmunol. Neuroinflamm., 2016, 3(4)e244
[72]
Popescu, B.F.G.; Lucchinetti, C.F. Pathology of demyelinating diseases. Annu. Rev. Pathol., 2012, 7(1), 185-217.
[http://dx.doi.org/10.1146/annurev-pathol-011811-132443] [PMID: 22313379]
[73]
Ontaneda, D.; Hyland, M.; Cohen, J.A. Multiple sclerosis: new insights in pathogenesis and novel therapeutics. Annu. Rev. Med., 2012, 63(1), 389-404.
[http://dx.doi.org/10.1146/annurev-med-042910-135833] [PMID: 21888515]
[74]
Engelhardt, B.; Ransohoff, R.M. The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol., 2005, 26(9), 485-495.
[http://dx.doi.org/10.1016/j.it.2005.07.004] [PMID: 16039904]
[75]
Hosmane, S.; Tegenge, M.A.; Rajbhandari, L.; Uapinyoying, P.; Ganesh Kumar, N.; Thakor, N.; Venkatesan, A. Toll/interleukin-1 receptor domain-containing adapter inducing interferon-β mediates microglial phagocytosis of degenerating axons. J. Neurosci., 2012, 32(22), 7745-7757.
[http://dx.doi.org/10.1523/JNEUROSCI.0203-12.2012] [PMID: 22649252]
[76]
Khorooshi, R.; Owens, T. Injury-induced type I IFN signaling regulates inflammatory responses in the central nervous system. J. Immunol., 2010, 185(2), 1258-1264.
[http://dx.doi.org/10.4049/jimmunol.0901753] [PMID: 20562259]
[77]
Galligan, C.L.; Pennell, L.M.; Murooka, T.T.; Baig, E.; Majchrzak-Kita, B.; Rahbar, R.; Fish, E.N. Interferon-β is a key regulator of proinflammatory events in experimental autoimmune encephalomyelitis. Mult. Scler., 2010, 16(12), 1458-1473.
[http://dx.doi.org/10.1177/1352458510381259] [PMID: 20935030]
[78]
Teige, I.; Treschow, A.; Teige, A.; Mattsson, R.; Navikas, V.; Leanderson, T.; Holmdahl, R.; Issazadeh-Navikas, S. IFN-beta gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis. J. Immunol., 2003, 170(9), 4776-4784.
[http://dx.doi.org/10.4049/jimmunol.170.9.4776] [PMID: 12707359]
[79]
Salem, M.; Mony, J.T.; Løbner, M.; Khorooshi, R.; Owens, T. Interferon regulatory factor-7 modulates experimental autoimmune encephalomyelitis in mice. J. Neuroinflammation, 2011, 8(1), 181-181.
[http://dx.doi.org/10.1186/1742-2094-8-181] [PMID: 22196084]
[80]
Wingerchuk, D.M.; Carter, J.L. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin. Proc., 2014, 89(2), 225-240.
[http://dx.doi.org/10.1016/j.mayocp.2013.11.002] [PMID: 24485135]
[81]
Rodero, M.P.; Crow, Y.J. Type I interferon-mediated monogenic autoinflammation: The type I interferonopathies, a conceptual overview. J. Exp. Med., 2016, 213(12), 2527-2538.
[http://dx.doi.org/10.1084/jem.20161596] [PMID: 27821552]
[82]
Li, Y.; Wilson, H.L.; Kiss-Toth, E. Regulating STING in health and disease. J. Inflamm. (Lond.), 2017, 14(1), 11-11.
[http://dx.doi.org/10.1186/s12950-017-0159-2] [PMID: 28596706]
[83]
Melki, I.; Rose, Y.; Uggenti, C.; Van Eyck, L.; Frémond, M.L.; Kitabayashi, N.; Rice, G.I.; Jenkinson, E.M.; Boulai, A.; Jeremiah, N.; Gattorno, M.; Volpi, S.; Sacco, O.; Terheggen-Lagro, S.W.J.; Tiddens, H.A.W.M.; Meyts, I.; Morren, M.A.; De Haes, P.; Wouters, C.; Legius, E.; Corveleyn, A.; Rieux-Laucat, F.; Bodemer, C.; Callebaut, I.; Rodero, M.P.; Crow, Y.J. Disease-associated mutations identify a novel region in human STING necessary for the control of type I interferon signaling. J. Allergy Clin. Immunol., 2017, 140(2), 543-552.e5.
[http://dx.doi.org/10.1016/j.jaci.2016.10.031] [PMID: 28087229]
[84]
Bialas, A.R.; Presumey, J.; Das, A.; van der Poel, C.E.; Lapchak, P.H.; Mesin, L.; Victora, G.; Tsokos, G.C.; Mawrin, C.; Herbst, R.; Carroll, M.C. Microglia-dependent synapse loss in type I interferon-mediated lupus. Nature, 2017, 546(7659), 539-543.
[http://dx.doi.org/10.1038/nature22821] [PMID: 28614301]
[85]
Crow, Y.J.; Manel, N. Aicardi-Goutières syndrome and the type I interferonopathies. Nat. Rev. Immunol., 2015, 15(7), 429-440.
[http://dx.doi.org/10.1038/nri3850] [PMID: 26052098]
[86]
Liu, Y.; Jesus, A.A.; Marrero, B.; Yang, D.; Ramsey, S.E.; Sanchez, G.A.M.; Tenbrock, K.; Wittkowski, H.; Jones, O.Y.; Kuehn, H.S.; Lee, C.R.; DiMattia, M.A.; Cowen, E.W.; Gonzalez, B.; Palmer, I.; DiGiovanna, J.J.; Biancotto, A.; Kim, H.; Tsai, W.L.; Trier, A.M.; Huang, Y.; Stone, D.L.; Hill, S.; Kim, H.J.; St Hilaire, C.; Gurprasad, S.; Plass, N.; Chapelle, D.; Horkayne-Szakaly, I.; Foell, D.; Barysenka, A.; Candotti, F.; Holland, S.M.; Hughes, J.D.; Mehmet, H.; Issekutz, A.C.; Raffeld, M.; McElwee, J.; Fontana, J.R.; Minniti, C.P.; Moir, S.; Kastner, D.L.; Gadina, M.; Steven, A.C.; Wingfield, P.T.; Brooks, S.R.; Rosenzweig, S.D.; Fleisher, T.A.; Deng, Z.; Boehm, M.; Paller, A.S.; Goldbach-Mansky, R. Activated STING in a vascular and pulmonary syndrome. N. Engl. J. Med., 2014, 371(6), 507-518.
[http://dx.doi.org/10.1056/NEJMoa1312625] [PMID: 25029335]
[87]
Abdullah, A.; Zhang, M.; Frugier, T.; Bedoui, S.; Taylor, J.M.; Crack, P.J. STING-mediated type-I interferons contribute to the neuroinflammatory process and detrimental effects following traumatic brain injury. J. Neuroinflammation, 2018, 15(1), 323.
[http://dx.doi.org/10.1186/s12974-018-1354-7] [PMID: 30463579]
[88]
Barrett, J.P.; Henry, R.J.; Shirey, K.A.; Doran, S.J.; Makarevich, O.D.; Ritzel, R.M.; Meadows, V.A.; Vogel, S.N.; Faden, A.I.; Stoica, B.A.; Loane, D.J. Interferon-β plays a detrimental role in experimental traumatic brain injury by enhancing neuroinflammation that drives chronic neurodegeneration. J. Neurosci., 2020, 40(11), 2357-2370.
[http://dx.doi.org/10.1523/JNEUROSCI.2516-19.2020] [PMID: 32029532]
[89]
Nazmi, A.; Field, R.H.; Griffin, E.W.; Haugh, O.; Hennessy, E.; Cox, D.; Reis, R.; Tortorelli, L.; Murray, C.L.; Lopez-Rodriguez, A.B.; Jin, L.; Lavelle, E.C.; Dunne, A.; Cunningham, C. Chronic neurodegeneration induces type I interferon synthesis via STING, shaping microglial phenotype and accelerating disease progression. Glia, 2019, 67(7), 1254-1276.
[http://dx.doi.org/10.1002/glia.23592] [PMID: 30680794]
[90]
Li, Q.; Cao, Y.; Dang, C.; Han, B.; Han, R.; Ma, H.; Hao, J.; Wang, L. Inhibition of double-strand DNA-sensing cGAS ameliorates brain injury after ischemic stroke. EMBO Mol. Med., 2020, 12(4)e11002
[http://dx.doi.org/10.15252/emmm.201911002] [PMID: 32239625]
[91]
Ryu, J.K.; Rafalski, V.A.; Meyer-Franke, A.; Adams, R.A.; Poda, S.B.; Rios Coronado, P.E.; Pedersen, L.O.; Menon, V.; Baeten, K.M.; Sikorski, S.L.; Bedard, C.; Hanspers, K.; Bardehle, S.; Mendiola, A.S.; Davalos, D.; Machado, M.R.; Chan, J.P.; Plastira, I.; Petersen, M.A.; Pfaff, S.J.; Ang, K.K.; Hallenbeck, K.K.; Syme, C.; Hakozaki, H.; Ellisman, M.H.; Swanson, R.A.; Zamvil, S.S.; Arkin, M.R.; Zorn, S.H.; Pico, A.R.; Mucke, L.; Freedman, S.B.; Stavenhagen, J.B.; Nelson, R.B.; Akassoglou, K. Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration. Nat. Immunol., 2018, 19(11), 1212-1223.
[http://dx.doi.org/10.1038/s41590-018-0232-x] [PMID: 30323343]
[92]
Rivest, S. Regulation of innate immune responses in the brain. Nat. Rev. Immunol., 2009, 9(6), 429-439.
[http://dx.doi.org/10.1038/nri2565] [PMID: 19461673]
[93]
Ransohoff, R.M.; Brown, M.A. Innate immunity in the central nervous system. J. Clin. Invest., 2012, 122(4), 1164-1171.
[http://dx.doi.org/10.1172/JCI58644] [PMID: 22466658]
[94]
Liu, D.; Wu, H.; Wang, C.; Li, Y.; Tian, H.; Siraj, S.; Sehgal, S.A.; Wang, X.; Wang, J.; Shang, Y.; Jiang, Z.; Liu, L.; Chen, Q. STING directly activates autophagy to tune the innate immune response. Cell Death Differ., 2019, 26(9), 1735-1749.
[http://dx.doi.org/10.1038/s41418-018-0251-z] [PMID: 30568238]
[95]
Wang, Z.; Chen, J.; Hu, J.; Zhang, H.; Xu, F.; He, W.; Wang, X.; Li, M.; Lu, W.; Zeng, G.; Zhou, P.; Huang, P.; Chen, S.; Li, W.; Xia, L.P.; Xia, X. cGAS/STING axis mediates a topoisomerase II inhibitor-induced tumor immunogenicity. J. Clin. Invest., 2019, 129(11), 4850-4862.
[http://dx.doi.org/10.1172/JCI127471] [PMID: 31408442]
[96]
Wang, Y.Y.; Shen, D.; Zhao, L.J.; Zeng, N.; Hu, T.H. Sting is a critical regulator of spinal cord injury by regulating microglial inflammation via interacting with TBK1 in mice. Biochem. Biophys. Res. Commun., 2019, 517(4), 741-748.
[http://dx.doi.org/10.1016/j.bbrc.2019.07.125] [PMID: 31400857]

Rights & Permissions Print Cite
Article Metrics
66
2
© 2024 Bentham Science Publishers | Privacy Policy