Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2016

Open Access 01-12-2016 | Research

Increased occurrence of protein kinase CK2 in astrocytes in Alzheimer’s disease pathology

Authors: Andrea F. N. Rosenberger, Tjado H. J. Morrema, Wouter H. Gerritsen, Elise S. van Haastert, Hripsime Snkhchyan, Riet Hilhorst, Annemieke J. M. Rozemuller, Philip Scheltens, Saskia M. van der Vies, Jeroen J. M. Hoozemans

Published in: Journal of Neuroinflammation | Issue 1/2016

Login to get access

Abstract

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disease. In addition to the occurrence of amyloid deposits and widespread tau pathology, AD is associated with a neuroinflammatory response characterized by the activation of microglia and astrocytes. Protein kinase 2 (CK2, former casein kinase II) is involved in a wide variety of cellular processes. Previous studies on CK2 in AD showed controversial results, and the involvement of CK2 in neuroinflammation in AD remains elusive.

Methods

In this study, we used immunohistochemical and immunofluorescent staining methods to investigate the localization of CK2 in the hippocampus and temporal cortex of patients with AD and non-demented controls. We compared protein levels with Western blotting analysis, and we investigated CK2 activity in human U373 astrocytoma cells and human primary adult astrocytes stimulated with IL-1β or TNF-α.

Results

We report increased levels of CK2 in the hippocampus and temporal cortex of AD patients compared to non-demented controls. Immunohistochemical analysis shows CK2 immunoreactivity in astrocytes in AD and control cases. In AD, the presence of CK2 immunoreactive astrocytes is increased. CK2 immunopositive astrocytes are associated with amyloid deposits, suggesting an involvement of CK2 in the neuroinflammatory response. In U373 cells and human primary astrocytes, the selective CK2 inhibitor CX-4945 shows a dose-dependent reduction of the IL-1β or TNF-α induced MCP-1 and IL-6 secretion.

Conclusions

This data suggests that CK2 in astrocytes is involved in the neuroinflammatory response in AD. The reduction in pro-inflammatory cytokine secretion by human astrocytes using the selective CK2 inhibitor CX-4945 indicates that CK2 could be a potential target to modulate neuroinflammation in AD.
Appendix
Available only for authorised users
Literature
1.
Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001;81:741–66.PubMed
2.
Carrano A, Hoozemans JJM, Van Der Vies SM, Van Horssen J, De Vries HE, Rozemuller AJM. Neuroinflammation and blood-brain barrier changes in capillary amyloid angiopathy. Neurodegener Dis. 2012;10:329–31.CrossRefPubMed
3.
Thal DR, Ghebremedhin E, Rüb U, Yamaguchi H, Del Tredici K, Braak H. Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol. 2002;61:282–93.PubMed
4.
Hoozemans JJM, Van Haastert ES, Mulder SD, Nielsen HM, Veerhuis R, Ruijtenbeek R, et al. Increased IRAK-4 kinase activity in Alzheimer’s disease; inhibitory effect of IRAK-1/4 inhibitor I on pro-inflammatory cytokine secretion but not on uptake of amyloid beta by human glial cells. J Clin Cell Immunol. 2014;5:243.
5.
6.
Arends YM, Duyckaerts C, Rozemuller JM, Eikelenboom P, Hauw JJ. Microglia, amyloid and dementia in Alzheimer disease: a correlative study. Neurobiol Aging. 2000;21:39–47.CrossRefPubMed
7.
Vehmas AK, Kawas CH, Stewart WF, Troncoso JC. Immune reactive cells in senile plaques and cognitive decline in Alzheimer’s disease. Neurobiol Aging. 2003;24:321–31.CrossRefPubMed
8.
Hoozemans JJM, van Haastert ES, Veerhuis R, Arendt T, Scheper W, Eikelenboom P, et al. Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer’s disease. J Neuroinflammation. 2005;2:27.CrossRefPubMedPubMedCentral
9.
Lambert J-C, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet. 2009;41:1094–9.CrossRefPubMed
10.
Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Marian L, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’ s disease. Nat Genet. 2009;41:1088–93.CrossRefPubMedPubMedCentral
11.
Naj AC, Jun G, Beecham GW, Wang L-S, Vardarajan BN, Buros J, et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet. 2011;43:436–41.CrossRefPubMedPubMedCentral
12.
Hollingworth P, Harold D, Sims R, Gerrish A, Lambert J-C, Carrasquillo MM, et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet. 2011;43:429–35.CrossRefPubMedPubMedCentral
13.
Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med. 2013;368:107–16.CrossRefPubMedPubMedCentral
14.
15.
Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;918–934.
16.
Rosenberger AFN, Hilhorst R, Coart E, García Barrado L, Naji F, Rozemuller AJM, et al. Protein kinase activity decreases with higher Braak stages of Alzheimer’s disease pathology. J Alzheimers Dis. 2015.
17.
Cohen P. Protein kinases—the major drug targets of the twenty-first century? Nat Rev Drug Discov. 2002;1:309–15.CrossRefPubMed
18.
Iimoto DS, Masliah E, Deteresa R, Terry RD, Saitoh T. Aberrant casein kinase II in Alzheimer’s disease. Brain Res. 1990;507:273–80.CrossRefPubMed
19.
Allende JE, Allende CC. Protein kinases. 4. Protein kinase CK2: an enzyme with multiple substrates and a puzzling regulation. FASEB J. 1995;9:313–23.PubMed
20.
Perez DI, Gil C, Martinez A. Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases. Med Res Rev. 2011;31:924–54.CrossRefPubMed
21.
Kramerov AA, Saghizadeh M, Pan H, Kabosova A, Montenarh M, Ahmed K, et al. Expression of protein kinase CK2 in astroglial cells of normal and neovascularized retina. Am J Pathol. 2006;168:1722–36.CrossRefPubMedPubMedCentral
22.
Shi X, Potvin B, Huang T, Hilgard P, Spray DC, Suadicani SO, et al. A novel casein kinase 2 alpha-subunit regulates membrane protein traffic in the human hepatoma cell line HuH-7. J Biol Chem. 2001;276:2075–82.CrossRefPubMed
23.
Meggio F, Pinna LA. One-thousand-and-one substrates of protein kinase CK2? FASEB J. 2003;17:349–68.CrossRefPubMed
24.
25.
Hériché JK, Chambaz EM. Protein kinase CK2alpha is a target for the Abl and Bcr-Abl tyrosine kinases. Oncogene. 1998;17:13–8.CrossRefPubMed
26.
Singh NN, Ramji DP. Protein kinase CK2, an important regulator of the inflammatory response? J Mol Med (Berl). 2008;86:887–97.CrossRef
27.
Bird TA, Schooley K, Dower SK, Hagen H, Virca GD. Activation of nuclear transcription factor NF-κB by interleukin-1 is accompanied by casein kinase II-mediated phosphorylation of the p65 subunit. J Biol Chem. 1997;272:32606–12.CrossRefPubMed
28.
Lodie TA, Savedra R, Golenbock DT, Van Beveren CP, Maki RA, Fenton MJ. Stimulation of macrophages by lipopolysaccharide alters the phosphorylation state, conformation, and function of PU.1 via activation of casein kinase II. J Immunol. 1997;158:1848–56.PubMed
29.
Van Lint J, Agostinis P, Vandevoorde V, Haegeman G, Fiers W, Merlevede W, et al. Tumor necrosis factor stimulates multiple serine/threonine protein kinases in Swiss 3 T3 and L929 cells. Implication of casein kinase-2 and extracellular signal-regulated kinases in the tumor necrosis factor signal transduction pathway. J Biol Chem. 1992;267:25916–21.PubMed
30.
Sayed M, Kim SO, Salh BS, Issinger OG, Pelech SL. Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase. J Biol Chem. 2000;275:16569–73.CrossRefPubMed
31.
Parhar K, Morse J, Salh B. The role of protein kinase CK2 in intestinal epithelial cell inflammatory signaling. Int J Colorectal Dis. 2007;22:601–9.CrossRefPubMed
32.
Singh NN, Ramji DP. Transforming growth factor-beta-induced expression of the apolipoprotein E gene requires c-Jun N-terminal kinase, p38 kinase, and casein kinase 2. Arterioscler Thromb Vasc Biol. 2006;26:1323–9.CrossRefPubMed
33.
Zdunek M, Silbiger S, Lei J, Neugarten J. Protein kinase CK2 mediates TGF-beta1-stimulated type IV collagen gene transcription and its reversal by estradiol. Kidney Int. 2001;60:2097–108.CrossRefPubMed
34.
Mead JR, Hughes TR, Irvine SA, Singh NN, Ramji DP. Interferon-gamma stimulates the expression of the inducible cAMP early repressor in macrophages through the activation of casein kinase 2: a potentially novel pathway for interferon mediated inhibition of gene transcription. J Biol Chem. 2003;278:17741–51.CrossRefPubMed
35.
Harvey EJ, Li N, Ramji DP. Critical role for casein kinase 2 and phosphoinositide-3-kinase in the interferon-gamma-induced expression of monocyte chemoattractant protein-1 and other key genes implicated in atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27:806–12.CrossRefPubMed
36.
Duncan JS, Litchfield DW. Too much of a good thing: the role of protein kinase CK2 in tumorigenesis and prospects for therapeutic inhibition of CK2. Biochim Biophys Acta. 2008;1784:33–47.CrossRefPubMed
37.
Sarno S, Ruzzene M, Frascella P, Pagano MA, Meggio F, Zambon A, et al. Development and exploitation of CK2 inhibitors. Mol Cell Biochem. 2005;274:69–76.CrossRefPubMed
38.
Sarno S, Reddy H, Meggio F, Ruzzene M, Davies SP, Donella-Deana A, et al. Selectivity of 4,5,6,7-tetrabromobenzotriazole, an ATP site-directed inhibitor of protein kinase CK2 (‘casein kinase-2’). FEBS Lett. 2001;496:44–8.CrossRefPubMed
39.
Pierre F, Chua PC, O’Brien SE, Siddiqui-Jain A, Bourbon P, Haddach M, et al. Discovery and SAR of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer. J Med Chem. 2011;54:635–54.CrossRefPubMed
40.
Chon HJ, Bae KJ, Lee Y, Kim J. The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies. Front Pharmacol. 2015;6:70.CrossRefPubMedPubMedCentral
41.
Martins LR, Lúcio P, Melão A, Antunes I, Cardoso BA, Stansfield R, et al. Activity of the clinical-stage CK2-specific inhibitor CX-4945 against chronic lymphocytic leukemia. Leukemia. 2014;28:179–82.CrossRefPubMed
42.
Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112:389–404.CrossRefPubMedPubMedCentral
43.
Thal DR, Rüb U, Schultz C, Sassin I, Ghebremedhin E, Del Tredici K, et al. Sequence of Abeta-protein deposition in the human medial temporal lobe. J Neuropathol Exp Neurol. 2000;59:733–48.PubMed
44.
Thal DR, Walter J, Saido TC, Fändrich M. Neuropathology and biochemistry of Aβ and its aggregates in Alzheimer’s disease. Acta Neuropathol. 2015;129:167–82.CrossRefPubMed
45.
Reisberg B, Ferris SH, De Leon MJ, Crook T. The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982;139:1136–9.CrossRefPubMed
46.
Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement. 2012;8:1–13.CrossRefPubMedPubMedCentral
47.
Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol. 2014;128:755–66.CrossRefPubMedPubMedCentral
48.
49.
Spillantini MG, Crowther RA, Goedert M. Comparison of the neurofibrillary pathology in Alzheimer’s disease and familial presenile dementia with tangles. Acta Neuropathol. 1996;92:42–8.CrossRefPubMed
50.
de Groot CJ, Hulshof S, Hoozemans JJ, Veerhuis R. Establishment of microglial cell cultures derived from postmortem human adult brain tissue: immunophenotypical and functional characterization. Microsc Res Tech. 2001;54:34–9.CrossRefPubMed
51.
Hoozemans JJM, Veerhuis R, Janssen I, van Elk E-J, Rozemuller AJM, Eikelenboom P. The role of cyclo-oxygenase 1 and 2 activity in prostaglandin E(2) secretion by cultured human adult microglia: implications for Alzheimer’s disease. Brain Res. 2002;951:218–26.CrossRefPubMed
52.
Alley MC, Scudiero DA, Monks A, Hursey Czerwinski MLMJ, Fine DL, Abbott BJ, et al. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 1988;48:589–601.PubMed
53.
Ruzzene M, Penzo D, Pinna LA. Protein kinase CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells. Biochem J. 2002;364(Pt 1):41–7.CrossRefPubMedPubMedCentral
54.
Lieb K, Fiebich BL, Hüll M, Berger M, Bauer J. Potent inhibition of interleukin-6 expression in a human astrocytoma cell line by tenidap. Cell Tissue Res. 1997;288:251–7.CrossRefPubMed
55.
Blom MA, van Twillert MG, de Vries SC, Engels F, Finch CE, Veerhuis R, et al. NSAIDS inhibit the IL-1 beta-induced IL-6 release from human post-mortem astrocytes: the involvement of prostaglandin E2. Brain Res. 1997;777:210–8.CrossRefPubMed
56.
Blanquet PR. Casein kinase 2 as a potentially important enzyme in the nervous system. Prog Neurobiol. 2000;211–246.
57.
Faust M, Montenarh M. Subcellular localization of protein kinase CK2. Cell Tissue Res. 2000;301:329–40.CrossRefPubMed
58.
Chung HJ, Huang YH, Lau L-F, Huganir RL. Regulation of the NMDA receptor complex and trafficking by activity-dependent phosphorylation of the NR2B subunit PDZ ligand. J Neurosci. 2004;24:10248–59.CrossRefPubMed
59.
Kimura R, Matsuki N. Protein kinase CK2 modulates synaptic plasticity by modification of synaptic NMDA receptors in the hippocampus. J Physiol. 2008;586:3195–206.CrossRefPubMedPubMedCentral
60.
Lenzken SC, Stanga S, Lanni C, De Leonardis F, Govoni S, Racchi M. Recruitment of casein kinase 2 is involved in AbetaPP processing following cholinergic stimulation. J Alzheimers Dis. 2010;20:1133–41.PubMed
61.
Raftery M, Campbell R, Glaros EN, Rye K-A, Halliday GM, Jessup W, et al. Phosphorylation of apolipoprotein-E at an atypical protein kinase CK2 PSD/E site in vitro. Biochemistry. 2005;44:7346–53.CrossRefPubMed
62.
Walter J, Schindzielorz A, Hartung B, Haass C. Phosphorylation of the beta-amyloid precursor protein at the cell surface by ectocasein kinases 1 and 2. J Biol Chem. 2000;275:23523–9.CrossRefPubMed
63.
Baum L, Masliah E, Iimoto DS, Hansen LA, Halliday WC, Saitoh T. Casein kinase II is associated with neurofibrillary tangles but is not an intrinsic component of paired helical filaments. Brain Res. 1992;573:126–32.CrossRefPubMed
64.
Lim ACB, Tiu S-Y, Li Q, Qi RZ. Direct regulation of microtubule dynamics by protein kinase CK2. J Biol Chem. 2004;279:4433–9.CrossRefPubMed
65.
De Felice FG, Vieira MNN, Bomfim TR, Decker H, Velasco PT, Lambert MP, et al. Protection of synapses against Alzheimer’s-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A. 2009;106:1971–6.CrossRefPubMedPubMedCentral
66.
Aksenova MV, Burbaeva GS, Kandror KV, Kapkov DV, Stepanov AS. The decreased level of casein kinase 2 in brain cortex of schizophrenic and Alzheimer’s disease patients. FEBS Lett. 1991;279:55–7.CrossRefPubMed
67.
Saitoh T, Iimoto D. Aberrant protein phosphorylation and cytoarchitecture in Alzheimer’s disease. Prog Clin Biol Res. 1989;317:769–80.PubMed
68.
Masliah E, Iimoto DS, Mallory M, Albright T, Hansen L, Saitoh T. Casein kinase II alteration precedes tau accumulation in tangle formation. Am J Pathol. 1992;140:263–8.PubMedPubMedCentral
69.
Kramerov AA, Golub AG, Bdzhola VG, Yarmoluk SM, Ahmed K, Bretner M, et al. Treatment of cultured human astrocytes and vascular endothelial cells with protein kinase CK2 inhibitors induces early changes in cell shape and cytoskeleton. Mol Cell Biochem. 2011;349:125–37.CrossRefPubMedPubMedCentral
70.
Kramerov AA, Ahmed K, Ljubimov AV. Cell rounding in cultured human astrocytes and vascular endothelial cells upon inhibition of CK2 is mediated by actomyosin cytoskeleton alterations. J Cell Biochem. 2012;113:2948–56.CrossRefPubMedPubMedCentral
71.
Nielsen HM, Veerhuis R, Holmqvist B, Janciauskiene S. Binding and uptake of A beta1-42 by primary human astrocytes in vitro. Glia. 2009;57:978–88.CrossRefPubMed
72.
Thal DR, Schultz C, Dehghani F, Yamaguchi H, Braak H, Braak E. Amyloid beta-protein (Abeta)-containing astrocytes are located preferentially near N-terminal-truncated Abeta deposits in the human entorhinal cortex. Acta Neuropathol. 2000;100:608–17.CrossRefPubMed
73.
Seldin DC, Leder P. Casein kinase II alpha transgene-induced murine lymphoma: relation to theileriosis in cattle. Science. 1995;267:894–7.CrossRefPubMed
74.
Drygin D, Ho CB, Omori M, Bliesath J, Proffitt C, Rice R, et al. Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer. Biochem Biophys Res Commun. 2011;415:163–7.CrossRefPubMed
75.
Landesman-Bollag E, Song DH, Romieu-Mourez R, Sussman DJ, Cardiff RD, Sonenshein GE, et al. Protein kinase CK2: signaling and tumorigenesis in the mammary gland. Mol Cell Biochem. 2001;227:153–65.CrossRefPubMed
76.
Axtell RC, Xu L, Barnum SR, Raman C. CD5-CK2 binding/activation-deficient mice are resistant to experimental autoimmune encephalomyelitis: protection is associated with diminished populations of IL-17-expressing T cells in the central nervous system. J Immunol. 2006;177:8542–9.CrossRefPubMedPubMedCentral
77.
Wang D, Westerheide SD, Hanson JL, Baldwin AS. Tumor necrosis factor alpha-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II. J Biol Chem. 2000;275:32592–7.CrossRefPubMed
78.
79.
Faust RA, Tawfic S, Davis AT, Bubash LA, Ahmed K. Antisense oligonucleotides against protein kinase CK2-alpha inhibit growth of squamous cell carcinoma of the head and neck in vitro. Head Neck. 2000;22:341–6.CrossRefPubMed
80.
Pistorius K, Seitz G, Remberger K, Issinger OG. Differential CKII activities in human colorectal mucosa, adenomas and carcinomas. Onkologie. 1991;14:256–60.CrossRef
81.
Stalter G, Siemer S, Becht E, Ziegler M, Remberger K, Issinger OG. Asymmetric expression of protein kinase CK2 subunits in human kidney tumors. Biochem Biophys Res Commun. 1994;202:141–7.CrossRefPubMed
82.
O-charoenrat P, Rusch V, Talbot SG, Sarkaria I, Viale A, Socci N, et al. Casein kinase II alpha subunit and C1-inhibitor are independent predictors of outcome in patients with squamous cell carcinoma of the lung. Clin Cancer Res. 2004;10:5792–803.CrossRefPubMed
83.
Kim JS, Eom JI, Cheong J-W, Choi AJ, Lee JK, Yang WI, et al. Protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in acute myeloid leukemia. Clin Cancer Res. 2007;13:1019–28.CrossRefPubMed
84.
Yenice S, Davis AT, Goueli SA, Akdas A, Limas C, Ahmed K. Nuclear casein kinase 2 (CK-2) activity in human normal, benign hyperplastic, and cancerous prostate. Prostate. 1994;24:11–6.CrossRefPubMed
85.
Siddiqui-Jain A, Drygin D, Streiner N, Chua P, Pierre F, O'Brien SE, et al. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy. Cancer Res. 2010;70:10288–98.CrossRefPubMed
86.
87.
Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease—a double-edged sword. Neuron. 2002;35:419–32.CrossRefPubMed
88.
van Gool WA, Aisen PS, Eikelenboom P. Anti-inflammatory therapy in Alzheimer’s disease: is hope still alive? J Neurol. 2003;250:788–92.CrossRefPubMed
Metadata
Title
Increased occurrence of protein kinase CK2 in astrocytes in Alzheimer’s disease pathology
Authors
Andrea F. N. Rosenberger
Tjado H. J. Morrema
Wouter H. Gerritsen
Elise S. van Haastert
Hripsime Snkhchyan
Riet Hilhorst
Annemieke J. M. Rozemuller
Philip Scheltens
Saskia M. van der Vies
Jeroen J. M. Hoozemans
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-015-0470-x

Other articles of this Issue 1/2016

Journal of Neuroinflammation 1/2016 Go to the issue

Erratum

Erratum to: Exacerbation of blast-induced ocular trauma by an immune response

Short report

Tumor necrosis factor superfamily member APRIL contributes to fibrotic scar formation after spinal cord injury

Research

Microglial immunophenotype in dementia with Alzheimer’s pathology

Research

Brain radiation injury leads to a dose- and time-dependent recruitment of peripheral myeloid cells that depends on CCR2 signaling

Research

Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells

Research

Macrophage depletion reduced brain injury following middle cerebral artery occlusion in mice