Systemic upregulation of CD40 and CD40 ligand mRNA expression in multiple sclerosis

It is increasingly clear that the CD40 and CD40 ligand (CD40L) receptor-ligand pair mediates a crucial activation signal in both cell-mediated and humoral immune responses. Here, we detected mRNA levels of CD40 and CD40L in non-stimulated peripheral blood mononuclear cells in 46 patients with multiple sclerosis (MS) and 46 healthy controls by a competitive RT - PCR procedure allowing quantification without previous culture or antigenic stimulation. The levels of CD40 and CD40L mRNA were markedly increased in MS patients (P<0.0001) compared with healthy controls. There was no difference between clinical MS subgroups or stage of disease. Our findings indicate that, although MS is an organ specific disorder, an increased signaling via the CD40 and CD40L pathway may be present at the systemic level. The nature of this upregulation, whether primary or secondary to the organ-specific autoimmune response, is yet to be determined. Since interference with CD40/CD40L is an effective way to interfere with autoimmune model diseases such as experimental autoimmune encephalomyelitis, it may be relevant to investigate further the role of these molecules in the pathogenesis of MS.     

Platelet CD40L at the interface of adaptive immunity

Initiated by the finding that platelets express functional CD40 ligand (CD40L, CD154), many new roles for platelets have been discovered in unanticipated areas, including the immune response. When current literature is considered as a whole, the picture that is emerging begins to show that platelets are able to significantly affect, for better or worse, the overall health and condition of the mammalian host. Animal models have made significant contributions to our expanding knowledge of platelet function, much of which is anticipated to be clinically relevant. While still mostly circumstantial, the evidence supports a critical role for CD40L in many normal and disease processes.     

Differentiated Th1 autoreactive effector cells can induce experimental autoimmune encephalomyelitis in the absence of IL-12 and CD40/CD40L interactions.

IL-12 plays a critical role in the priming of Th1 responses to bacterial/parasitic antigens and autoantigens. Several studies have demonstrated a dependency on CD40/CD40L interactions and IL-12 for maintenance of both antibacterial/parasitic and autoreactive Th1 cells in vivo. However, it is still unclear if fully differentiated Th1 effectors require continued stimulation by IL-12. We demonstrate that the proliferative response and IFN-gamma production by a fully differentiated T cell line specific for myelin oligodendrocyte glycoprotein are completely independent of IL-12 and CD40/CD40L interactions. The capacity of this line to adoptively transfer experimental autoimmune encephalomyelitis is also independent of IL-12 and CD40/CD40L. These results have important implications regarding the therapeutic usefulness of blockade of IL-12 or the CD40/CD40L pathway for treatment of autoimmune disease.     

重症肌无力患者血清中可溶性CD40配体表达及临床意义

目的:研究重症肌无力(MG)患者血清中可溶性CD40配体(sCD40L)及抗乙酰胆碱受体抗体(AchRab)的水平,探讨sCD40L在MG发病中的作用。方法:研究对象为25例MG患者,分为急性期组13例,非急性期组12例,设正常对照组15例。取静脉血,分离血清,采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)测定血清中可溶性CD40配体及抗乙酰胆碱受体抗体(AchRab)的含量。结果:MG急性期组中sCD40L及AchRab的含量比非急性期组及正常对照组显著升高(P<0.01),非急性期组sCD40L及AchRab的含量比正常对照组显著升高(P<0.05)。各组sCD40L与AchRab均呈正相关。结论:sCD40L含量增高可能与MG发生和加重有关。     

Behavioral effects of CD40-CD40L pathway disruption in aged PSAPP mice

We have shown that, when an amyloid-beta peptide (Abeta) overproducing transgenic mouse model (PSAPP) of Alzheimer's disease (AD) is treated with a depleting antibody against CD40L, it causes marked attenuation of Abeta pathology associated with decreased amyloidogenic processing of amyloid precursor protein (APP) and increased cerebral clearance of Abeta. Here, we report that, when PSAPP mice receive a regimen of anti-CD40L antibody commencing at an age associated with initial Abeta deposition, they demonstrate superior spatial memory on the standard water maze and radial arm water maze tasks, as well as exhibiting superior non-spatial memory in the object recognition test, as compared to control PSAPP mice. Furthermore, PSAPP mice treated with an anti-CD40L antibody regimen commencing at an age associated with extensive Abeta deposition demonstrate superior spatial memory on the standard water maze task, as compared to control PSAPP mice. Disruption of CD40L activity has beneficial effects on pathology and cognitive behavior in the PSAPP mouse model, providing support for the therapeutic potential of interrupting the CD40-CD40L interaction in AD.     

CD40-CD40 L在颈动脉粥样硬化斑块稳定性中的作用及与基质金属蛋白酶的相关性

目的 观察CD40、CD40L和基质金属蛋白酶9(MMP9)在人类颈动脉粥样硬化斑块中的表达情况,探讨CD40、CD40L在斑块稳定性中的作用及与MMP9表达的关系.方法 将因颈动脉粥样硬化狭窄(>70%)行颈动脉内膜切除术的37例手术标本分为有临床脑卒中事件组(A组,n=20)和无临床脑卒中事件组(B组,n=17),另设尸检正常颈动脉(C组,n=11)作为对照组,采用实时荧光定量聚合酶链反应法检测各组斑块中CD40、CD40L和MMP9 mRNA水平,Western blot检测各组CD40、CD40L和MMP9蛋白表达水平,免疫组织化学检测各组CD40、CD40L和MMP9表达及分布,并对CD40、CD40L与MMP9的转录及表达水平作相关性分析.结果 A、B、C 3组的CD40mRNA的相对表达量分别为:2.41±0.43、1.03±0.38和0.31±0.12;MMP9 mRNA的相对表达量分别为:6.88±1.57、1.90±0.44和0.39±0.12.A组CD40、MMP9的mRNA水平高于B组(FCD40=105.183,FMMP9=160.395,P=0.000),B组高于C组(FCD40=37.307,FMMP9=124.093,P=0.000);CD40与MMP9的mRNA水平有正的直线相关关系(r=0.929,P=0.000),但各组CD40L的mRNA水平差异无统计学意义(FA-B=0.033,P=0.857;FB-C=1.564,P=0.767;FA-C=0.219,P=0.644).A组CD40、CD40L和MMP9的蛋白表达高于B组(FCD40=104.100,P=0.000;FCD40L=129.932,P=0.000;FMMP9=13.565,P=0.021),B组高于C组(FCD40=115.848,P=0.000;FCD40L=30.482,P=0.005;FMMP9=35.557,P=0.004).免疫组织化学示CD40、CD40L和MMP9的阳性表达面积A组大于B组(FCD40=39.451,FCD40L=57.606,FMMP9=30.711,P=0.000),B组大于C组(FCD40=95.066,FCD40L=59.081,FMMP9=145.758,P=0.000);CD40、CD40L与MMP9的阳性表达面积有正相关关系(rCD40L-CD40L=0.963,rCD40-MMP9=0.959,rCD40L-MMP9=0.929,P=0.000),并且CD40、CD40L和MMP9均在斑块肩部表达明显增多.结论 CD40-CD40L在动脉粥样硬化的形成和斑块稳定性中起重要作用;其可能通过上调MMP9导致斑块不稳定;CD40L可能是通过转录后修饰影响CD40L的表达,从而产生生物学效应.     

Chorioamnionitis is associated with increased CD40L expression on cord blood platelets

Chorioamnionitis (CA) is a severe infection responsible not only for premature birth but also for many severe neonatal diseases. The aim of the present study was to investigate the expression of CD40L and P-selectin on platelets and the plasma levels of their soluble forms in the umbilical cord blood in infants with documented chorioamnionitis. Umbilical cord blood samples were obtained from 10 healthy term newborns, 10 non-infected preterm infants, 10 preterm infants with premature rupture of membranes and 9 preterm infants with clinical and histological CA.The expression of CD40L and P-selectin on platelets was analyzed by flow cytometry. Soluble P-selectin (sCD62P), soluble CD40L (sCD40L) and interleukine-6 (IL-6) were measured in plasma by ELISA assays. Neonates with CA had significantly higher percentages of platelets expressing CD40L in basal conditions (5.3 +/- 2.9% vs. 1.6 +/- 0.7% and in non-infected preterm infants p < 0.05), while the percentages of P-selectin positive platelets were similar among all groups. In contrast, the level of sP-selectin was higher in infants with CA (222 +/- 128 ng/ml vs. 104 +/- 71 ng/ml in non-infected preterm infants, p < 0.05) but no differences were found in the levels of sCD40L. As expected, the levels of IL-6, a pro-inflammatory cytokine were significantly higher in samples obtained from preterm neonates whose mothers had also elevated inflammatory parameters. Our observations suggest that platelets are involved in the complex inflammatory pathogenesis of CA. Neither P-selectin expression on cord blood platelets nor plasma sP-selectin or sCD40L were suitable platelet markers in CA, whereas CD40L was significantly elevated in histologically proven CA.     

Cytokine regulation of CD40 expression in fetal human astrocyte cultures

CD40 can participate in inflammatory processes after binding its cognate ligand (CD40L). We found that fetal human astrocytes constitutively express CD40 mRNA and protein. Upon incubating cultures with proinflammatory cytokines (TNF-alpha, IL-1beta and IFN-gamma) or with lipopolysaccharide (LPS), CD40 expression was increased. No change in CD40 expression was noted in astrocyte cultures incubated with IL-6, HIV or gp41. Astrocytes also showed increased release of proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 after incubation with CD40L peptide. These observations suggest a role for CD40 in central nervous system (CNS) inflammation and that CD40/CD40L autocrine or paracrine pathways may mediate this role.     

Death receptor-mediated apoptosis in human malignant glioma cells: modulation by the CD40/CD40L system

CD40, a TNF-R-related cell surface receptor, is shown here to be expressed by glioma cells in vitro and in vivo. Glioma cell lines expressing low levels of CD40 at the cell surface resist cytotoxic effects of CD40L. CD40 gene transfer sensitizes glioma cells to CD40L. Inhibition of protein synthesis potentiates cell death which involves CD40 clustering and caspases 8 and 3 processing. CD40-transfected LN-18 cells acquire resistance to CD95L. In contrast, subtoxic concentrations of CD40L strongly sensitize these cells for TNF-alpha-induced apoptosis. Bispecific CD40xCD95 antibodies specifically kill glioma cells, disclosing the property of endogenous CD40 to facilitate death signalling.     

The role of CD40 in CD40L- and antibody-mediated platelet activation

Our initial finding that CD40- and CD40 ligand (CD40L)-deficient mice displayed prolonged tail bleeding and platelet function analyzer (PFA-100) closure times prompted us to further investigate the role of the CD40-CD40L dyad in primary hemostasis and platelet function. Recombinant human soluble CD40L (rhsCD40L), chemical cross-linking of which suggested a trimeric structure of the protein in solution, activated platelets in a CD40-dependent manner as evidenced by increased CD62P expression. CD40 monoclonal antibody (mAb) M3, which completely blocked rhsCD40L-induced platelet activation, also prolonged PFA-100 closure times of normal human blood. In contrast, CD40 mAb G28-5 showed less potential in blocking rhsCD40L-induced CD62P expression and did not affect PFA-100 closure times. However, when added to the platelets after rhsCD40L, G28-5 significantly enhanced the platelet response by causing clustering of, and signaling through, FcgammaRII. Similarly, higher order multimeric immune complexes formed at a 1/3 molar ratio of M90, a CD40L mAb, to rhsCD40L induced strong Fcgamma RII-mediated platelet activation when translocated to the platelet surface in a CD40-dependent manner, including the induction of morphological shape changes, fibrinogen binding, platelet aggregation, dense granule release, microparticle generation and monocyte-platelet-conjugate formation. The results suggest that CD40 may play a role in primary hemostasis and platelet biology by two independent mechanisms: First, by functioning as a primary signaling receptor for CD40L and, second, by serving as a docking molecule for CD40L immune complexes. The latter would also provide a potential mechanistic explanation for the unexpected high incidence of CD40L mAb-associated thrombotic events in recent human and animal studies.     

B cells play a cooperative role via CD40L-CD40 interaction in T cell-mediated experimental autoimmune neuritis in Lewis rats

The expression of co-stimulatory molecules CD40 and CD40L was examined over the course of experimental autoimmune neuritis (EAN) induced in Lewis rats by immunization with bovine peripheral nerve myelin. In draining lymph nodes, highest level of CD40L expression was seen on day 7 post immunization (p.i.), i.e. before onset of clinical signs of EAN, while CD40 expression was increased on day 14 p.i., i.e. at peak of clinical disease. In contrast, both CD40 and CD40L expressing cells in sciatic nerves, a target organ of EAN, peaked on day 14 p.i., large numbers of both expressing cells were mainly detected on day 14-21 p.i. After co-culture with EAN rat B cells bearing CD40, P0 peptide 180-199-specific T cell line cells exhibited a rapid down-regulation of CD40L expression. Furthermore, EAN rats had enhanced P0 peptide 180-199-specific antibody responses on day 14 p.i., which might have contributed to their aggravated EAN and further demonstrated the role of antibodies in EAN. The results indicate that CD40L-CD40 interactions are involved in the initiation of the antigen-specific T cell responses associated with the generation and development of EAN, and may mediate autoantibody production in EAN. Evidently, B cells play a cooperative role via CD40L-CD40 interaction in T cell-mediated EAN of Lewis rats.     

Induction of beta-chemokine secretion by human brain microvessel endothelial cells via CD40/CD40L interactions

beta-chemokines play an important role during the course of central nervous system (CNS) inflammation. Using primary cultures of human cerebral microvascular endothelial cells, we detected increased monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation normal T cell expressed and secreted (RANTES) production following incubation with soluble CD40L. These results suggest a potential mechanism by which activated CD40L positive T cells may enhance beta-chemokine expression and thus influence the recruitment of mononuclear cells across the human blood-brain barrier.     

Soluble CD40 and soluble CD40L concentrations in the serum and the cerebrospinal fluid of patients with tick borne encephalitis and neuroborreliosis

BACKGROUND AND PURPOSE: The interaction between CD40 and CD40L is essential in generating of an immunological response also intrathecally. The aim of the study was estimation of a concentration soluble form of CD40, CD40L (CD154) in the bacterial and viral inflammation of the central nervous system in two compartments - blood circulation and intrathecally, before and after the treatment. MATERIAL AND METHODS: sCD40 and sCD40L were tested twice before and after treatment in pairs serum and CSF of 40 patients treated in the Dept. of Infectious Diseases and Neuroinfections. Patients were divided in two groups: (n=20) patients with tick borne encephalitis (TBE) (group I, n=20) and patients with neuroborreliosis in the form of lymphocytic meningitis (group II, n=20). ELISA assays were performed. RESULTS: Significantly increased concentrations of sCD40, sCD40L in CSF (higher in neuroborreliosis) were measured. We found also an increased concentration of sCD40L in inflammatory CSF in both tested groups (in neuroboreliosis lasting also after 4 weeks of treatment), compared with the control group (below the detection limit in normal CSF). CONCLUSIONS: Results of estimation of the sCD40 and sCD40L concentrations indicate their role in the intrathecal inflammation process of bacterial and viral etiology. The increased serum concentration of sCD40L in TBE and CD40 in neuroborreliosis indicate that peripheral activation of the immunological system persists after cessation of treatment and after the clinical recovery. The defense mechanisms are more pronounced in neuroborreliosis than in tick borne encephalitis.     

Periodontopathogens induce expression of CD40L on human platelets via TLR2 and TLR4

Introduction

The outstanding importance of (soluble) CD40L to cardiovascular disease (CVD) is becoming increasingly apparent as CD40L is an important mediator of thrombotic and inflammatory processes. Platelets are the main source for CD40 ligand, linking platelet stimulatory events to inflammation and adverse adaptive immune responses. Periodontitis represents a chronic dental infection by distinct gram negative bacteria that is associated with an increased risk for CVD. However, the effects of periodontopathogens on CD40L expression by platelets have not been determined.

Material and Methods

Effects of periodontopathogens A. actinomycetemcomitans Y and P. gingivalis on the expression of CD40L were determined and the underlying receptors and pathways were investigated. 26 patients with periodontitis and 19 controls were included in the clinical part of this study.

Results

Periodontopathogens directly induce surface expression of CD40L in human platelets. This activation depends on plasma factors like CD14 and involves TLR2 and TLR4 but not FcγRII. Inhibition of PI3K and PLC completely abolishes bacteria-induced surface expression of CD40L. TLR2 and TLR4 agonists, for example, are also able to induce expression and release of CD40L in human platelets.In patients with periodontitis, plasma levels of soluble CD40L are elevated and positivity for P. gingivalis is associated with a statistical significant increase of soluble CD40L.

Conclusions

Our data indicate an involvement of periodontopathogens in increased plasma levels of soluble CD40L in periodontitis and therefore provide a novel link between periodontitis and increased risk for CVD.     

CD40L disruption enhances Abeta vaccine-mediated reduction of cerebral amyloidosis while minimizing cerebral amyloid angiopathy and inflammation

Amyloid-beta (Abeta) immunization efficiently reduces amyloid plaque load and memory impairment in transgenic mouse models of Alzheimer's disease (AD). Active Abeta immunization has also yielded favorable results in a subset of AD patients. However, a small percentage of patients developed severe aseptic meningoencephalitis associated with brain inflammation and infiltration of T-cells. We have shown that blocking the CD40-CD40 ligand (L) interaction mitigates Abeta-induced inflammatory responses and enhances Abeta clearance. Here, we utilized genetic and pharmacologic approaches to test whether CD40-CD40L blockade could enhance the efficacy of Abeta(1-42) immunization, while limiting potentially damaging inflammatory responses. We show that genetic or pharmacologic interruption of the CD40-CD40L interaction enhanced Abeta(1-42) immunization efficacy to reduce cerebral amyloidosis in the PSAPP and Tg2576 mouse models of AD. Potentially deleterious pro-inflammatory immune responses, cerebral amyloid angiopathy (CAA) and cerebral microhemorrhage were reduced or absent in these combined approaches. Pharmacologic blockade of CD40L decreased T-cell neurotoxicity to Abeta-producing neurons. Further reduction of cerebral amyloidosis in Abeta-immunized PSAPP mice completely deficient for CD40 occurred in the absence of Abeta immunoglobulin G (IgG) antibodies or efflux of Abeta from brain to blood, but was rather correlated with anti-inflammatory cytokine profiles and reduced plasma soluble CD40L. These results suggest CD40-CD40L blockade promotes anti-inflammatory cellular immune responses, likely resulting in promotion of microglial phagocytic activity and Abeta clearance without generation of neurotoxic Abeta-reactive T-cells. Thus, combined approaches of Abeta immunotherapy and CD40-CD40L blockade may provide for a safer and more effective Abeta vaccine.     

Differences of soluble CD40L in sera and plasma: implications on CD40L assay as a marker of thrombotic risk

INTRODUCTION: Soluble CD40L (sCD40L) ELISA has emerged as a promising predictor of poor outcomes in acute coronary syndrome. Yet many blood processing techniques have been used with little consideration of their effect on the results. METHODS: We measured sCD40L by ELISA in 10 patients with thrombocytopenia and 12 with normal or high platelet counts and 8 healthy controls using three sampling techniques: serum clotted on ice (serum-I) or at room temperature (serum-RT) and platelet poor plasma (PPP). RESULTS: Serum-RT samples, compared to serum-I, gave significantly higher CD40L values (p=0.003), demonstrating that ex vivo sCD40L release by activated platelets is inhibited by cold temperature. Although serum-I and PPP were comparable in patients with normal platelet counts, serum-I gave significantly higher values than PPP in the thrombocytosis group (p=0.01), suggesting that cold inhibition is insufficient in the latter group. To estimate the fraction of sCD40L that was microparticle-bound CD40L (mp-CD40L), 16 samples underwent 0.1-microm filtration. 50.6% of sCD40L was mp-CD40L in serum-RT, whereas 21.3% and 29.9% were observed in serum-I and PPP, respectively. Lastly, plasma sCD40L was assayed in 46 patients with and 35 without thrombosis. Plasma sCD40L did not correlate with platelet count in non-thrombotic, non-inflammatory patients but did (p<0.01) in those with thrombosis. CONCLUSIONS: Sample processing and temperature profoundly affect sCD40L assay. Serum-I and PPP minimize the release of sCD40L ex vivo and better represent sCD40L in vivo. However, PPP may be preferable particularly in patients with thrombocytosis. The existence of mp-CD40L highlights the importance of centrifuge conditions.     

The CD40/CD40L system regulates rat cerebral microvasculature after focal ischemia/reperfusion via the mTOR/S6K signaling pathway

Objective: The role of CD40/CD40 ligand (CD40L) in microvascular thrombosis is now widely accepted. However, the exact mechanisms linking the CD40/CD40L system and the soluble form of CD40L (sCD40L) with microvascular thrombosis are currently a topic of intensive research. The objective of this study was to assess the potential mechanisms in CD40/CD40L system-regulated microvascular thrombosis after focal ischemia/reperfusion (I/R).

Methods: Rats were subjected to 60-min transient middle cerebral artery occlusion (MCAO). The experiments were divided into three groups: sham operation, MCAO, and MCAO + CD40 antagonist. Dynamic changes of serum-free sCD40L levels for 0, 1, 3, 5, 6, and 12 h by ELISA detecting kit after focal I/R were observed, and the CD40 expression levels in both platelet surface and vascular endothelial cell surface were measured by flow cytometry and immunofluorescence, respectively. Cerebral infarct volume was analyzed 12 h after reperfusion. mTOR/S6K signaling was determined by Western blot.

Results: A comparison of thrombus formation between MCAO and CD40 antagonist treatment rats revealed a role for CD40 and/or CD40L in the inflammation-enhanced thrombosis responses in both of the platelet and vascular endothelial cell. MCAO rats yielded an acceleration of thrombus formation that was accompanied by increased CD40 levels in serum. The brain infarction was significantly decreased in CD40 antagonist treatment group compared to MCAO model group. The mTOR/S6K signaling was activated in MACO model than that of CD40 antagonist treatment group.

Conclusions: Our findings indicate that CD40/CD40L system contributes to microvascular thrombosis and brain infarction induced by MCAO and reperfusion. The mTOR/S6K signaling pathway is involved in the regulation of cerebral microvasculature after focal I/R by CD40/CD40L.

Abbreviations:

AKT: protein kinase B; CD40L: CD40 ligand; CSF: cerebrospinal fluid; FITC: fluorescein isothiocyanate; I/R: ischemia/reperfusion; MCAO: middle cerebral artery occlusion; mTOR: mechanistic target of rapamycin; PE: P-phycoerythrin; sCD40L: soluble form of CD40L; TNF-a: tumor necrosis factor-alpha; WT: wild type.     

CD40L deletion delays neuronal death in a model of neurodegeneration due to mild impairment of oxidative metabolism

Inflammatory/immune processes are important in the pathogenesis of neurodegenerative diseases. Thiamine deficiency (TD) models the region selective neuronal loss in brain that accompanies mild impairment of oxidative metabolism. TD induces well-defined alterations in neurons, microglia, astrocytes, and endothelial cells. To test the role of inflammatory/immune mechanisms in TD-induced neurodegeneration, the temporal profile of neurodegeneration was compared to the activation of CD68-positive microglia and ICAM-1-positive endothelial cells during TD in wild type mice and in CD40L-/- mice. CD40L-/- delayed the onset of TD-induced neuronal death as well as the activation of microglia and endothelial cells. The current results suggest that CD40L-mediated immune and inflammatory responses have a role in TD-induced neuronal death.     

CD40 promotion of amyloid beta production occurs via the NF-kappaB pathway

The CD40 receptor is a member of the tumor necrosis factor (TNF) super-family of trans-membrane receptors. Interaction of CD40 with its ligand CD40L mediates a broad range of immune and inflammatory responses in the periphery and in the central nervous system. Recently it has been suggested that CD40/CD40L interaction is involved in amyloid precursor protein (APP) processing and Alzheimer's disease (AD)-like pathology in transgenic mouse models of AD. We have previously shown that pharmacologically inhibiting CD40/CD40L interaction improves memory deficits in the PSAPP AD mouse model. We have also recently shown that CD40 deficiency mitigates amyloid deposition in APPsw and PSAPP mouse models. In the present report, using human embryonic kidney cells (HEK293) over-expressing both the APPsw mutation and CD40, we demonstrate that CD40/CD40L interaction directly increases the production of APP metabolites (Abeta 1-40, Abeta 1-42, CTFs, sAPPbeta and sAPPalpha). The results also show that CD40/CD40L interaction affects APP processing via the NF-kappaB pathway. Using NFkappaB inhibitors and SiRNAs to silence diverse elements of the NFkappaB pathway, we observe a reduction in levels of both Abeta 1-40 and Abeta 1-42. Taken together, our results further suggest that CD40L stimulation may be a key component in AD pathology and that elements of the NF-kappaB pathway may be suitable targets for therapeutic approaches against AD.     

Decreased mRNA Expressions of CD40L in Patients with Neuromyelitis Optica Spectrum Disorder

Journal of Molecular Neuroscience - Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease that preferentially affects central nerve system. Herein, we evaluated changes of CD40L...