Signaling Pathways In Pathogenesis Research Articles

The exo-microRNA (miRNA) signaling pathways in pathogenesis and treatment of stroke diseases: Emphasize on mesenchymal stem cells (MSCs).

A major factor in long-term impairment is stroke. Patients with persistent stroke and severe functional disabilities have few therapy choices. Longnoncoding RNAs (lncRNAs) may contribute to the regulation of the pathophysiologic processes of ischemic stroke as shown by altered expression of lncRNAsand microRNA (miRNAs) in blood samples of acute ischemic stroke patients. On the other hand, multipotent mesenchymal stem cells (MSCs) increase neurogenesis, and angiogenesis, dampen neuroinflammation, and boost brain plasticity to improve functional recovery in experimental stroke models. MSCs can be procured from various sources such as the bone marrow, adipose tissue, and peripheral blood. Under the proper circumstances, MSCs can differentiate into a variety of mature cells, including neurons, astrocytes, and oligodendrocytes. Accordingly, the capability of MSCs to exert neuroprotection and also neurogenesis has recently attracted more attention. Nowadays, lncRNAs and miRNAs derived from MSCs have opened new avenues to alleviate stroke symptoms. Accordingly, in this review article, we examined various studies concerning the lncRNAs and miRNAs'role in stroke pathogenesis and delivered an overview of the therapeutic role of MSC-derived miRNAs and lncRNAs in stroke conditions.

The Role of the Notch Signaling Pathway in Pathogenesis of Lung Diseases with Noninfectious Etiology

The Role of the Notch Signaling Pathway in Pathogenesis of Lung Diseases with Noninfectious Etiology

Role of JAK-STAT signaling pathway in pathogenesis and treatment of primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with high prevalence and possible poor prognosis. Though the pathogenesis of pSS has not been fully elucidated, B cell hyperactivity is considered as one of the fundamental abnormalities in pSS patients. It has long been identified that Janus kinases-signal transducer and activator of transcription (JAK-STAT) signaling pathway contributes to rheumatoid arthritis and systemic lupus erythematosus. Recently, increasing numbers of studies have provided evidence that JAK-STAT pathway also has an important role in the pathogenesis of pSS via direct or indirect activation of B cells. Signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5 activated by various cytokines and ribonucleic acid contribute to pSS development, respectively or synergically. These results reveal the potential application of Janus kinase inhibitors for treatment of pSS, which may fundamentally improve the quality of life and prognosis of patients with pSS.

Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.

Thoracic aortic disease affects people of all ages and the majority of those aged <60 years have an underlying genetic cause. There is presently no effective medical therapy for thoracic aneurysm and surgery remains the principal intervention. Unlike abdominal aortic aneurysm, for which the inflammatory/atherosclerotic pathogenesis is well established, the mechanism of thoracic aneurysm is less understood. This paper examines the key cell signaling systems responsible for the growth and development of the aorta, homeostasis of endothelial and vascular smooth muscle cells and interactions between pathways. The evidence supporting a role for individual signaling pathways in pathogenesis of thoracic aortic aneurysm is examined and potential novel therapeutic approaches are reviewed. Several key signaling pathways, notably TGF-β, WNT, NOTCH, PI3K/AKT and ANGII contribute to growth, proliferation, cell phenotype and survival for both vascular smooth muscle and endothelial cells. There is crosstalk between pathways, and between vascular smooth muscle and endothelial cells, with both synergistic and antagonistic interactions. A common feature of the activation of each is response to injury or abnormal cell stress. Considerable experimental evidence supports a contribution of each of these pathways to aneurysm formation. Although human information is less, there is sufficient data to implicate each pathway in the pathogenesis of human thoracic aneurysm. As some pathways i.e., WNT and NOTCH, play key roles in tissue growth and organogenesis in early life, it is possible that dysregulation of these pathways results in an abnormal aortic architecture even in infancy, thereby setting the stage for aneurysm development in later life. Given the fine tuning of these signaling systems, functional polymorphisms in key signaling elements may set up a future risk of thoracic aneurysm. Multiple novel therapeutic agents have been developed, targeting cell signaling pathways, predominantly in cancer medicine. Future investigations addressing cell specific targeting, reduced toxicity and also less intense treatment effects may hold promise for effective new medical treatments of thoracic aortic aneurysm.

Exploring the pathogenesis linking traumatic brain injury and epilepsy via bioinformatic analyses.

Traumatic brain injury (TBI) is a serious disease that could increase the risk of epilepsy. The purpose of this article is to explore the common molecular mechanism in TBI and epilepsy with the aim of providing a theoretical basis for the prevention and treatment of post-traumatic epilepsy (PTE). Two datasets of TBI and epilepsy in the Gene Expression Omnibus (GEO) database were downloaded. Functional enrichment analysis, protein-protein interaction (PPI) network construction, and hub gene identification were performed based on the cross-talk genes of aforementioned two diseases. Another dataset was used to validate these hub genes. Moreover, the abundance of infiltrating immune cells was evaluated through Immune Cell Abundance Identifier (ImmuCellAI). The common microRNAs (miRNAs) between TBI and epilepsy were acquired via the Human microRNA Disease Database (HMDD). The overlapped genes in cross-talk genes and target genes predicted through the TargetScan were obtained to construct the common miRNAs-mRNAs network. A total of 106 cross-talk genes were screened out, including 37 upregulated and 69 downregulated genes. Through the enrichment analyses, we showed that the terms about cytokine and immunity were enriched many times, particularly interferon gamma signaling pathway. Four critical hub genes were screened out for co-expression analysis. The miRNA-mRNA network revealed that three miRNAs may affect the shared interferon-induced genes, which might have essential roles in PTE. Our study showed the potential role of interferon gamma signaling pathway in pathogenesis of PTE, which may provide a promising target for future therapeutic interventions.

Circulatory Endothelin 1-Regulating RNAs Panel: Promising Biomarkers for Non-Invasive NAFLD/NASH Diagnosis and Stratification: Clinical and Molecular Pilot Study.

Nonalcoholic fatty liver disease (NAFLD) is one of the major seeds of liver cirrhosis and hepatocellular carcinoma. There is no convenient reliable non-invasive early diagnostic tool available for NAFLD/NASH diagnosis and stratification. Recently, the role of cytosolic sensor, stimulator of interferon genes (STING) signaling pathway in pathogenesis of nonalcoholic steatohepatitis (NASH) has been evidenced in research. We have selected EDN1/TNF/MAPK3/EP300/hsa-miR-6888-5p/lncRNA RABGAP1L-DT-206 RNA panel from bioinformatics microarrays databases related to STING pathway and NAFLD/NASH pathogenesis. We have used reverse-transcriptase real-time polymerase chain reaction to assess the expression of the serum RNAs panel in NAFLD/NASH without suspicion of advanced fibrosis, NAFLD/with NASH patients with suspicion of advanced fibrosis and controls. Additionally, we have assessed the diagnostic performance of the Ribonucleic acid (RNA) panel. We have detected upregulation of the EDN1 regulating RNAs panel expression in NAFLD/NASH cases compared to healthy controls. We concluded that this circulatory RNA panel could enable us to discriminate NAFLD/NASH cases from controls, and also NAFLD/NASH cases (F1, F2) from advanced fibrosis stages (F3, F4).

Insight of Mechanism and Signaling Pathway in Pathogenesis of Diabetic Neuropathy: A Review

Diabetic neuropathy (DN) is a common chronic microvascular complication of diabetes mellitus. The features of DN include allodynia, hyperalgesia, abnormal or loss of sensation of nerve fibers. The clinical features will contribute to poor quality of life, disrupt sleep, lead to depression, and increases mortality. Current drug treatments have been shown to alleviate the symptoms of DN but failed to treat the underlying causes of DN. Therefore, a better understanding of the molecular mechanisms underlying the development and progression of DN is needed for early diagnosis and intervention and understanding the failure of existing treatments. Identification of potential mechanisms is critical for better prediction of progression and for designing preventive therapies. DN's exact pathogenesis is incomplete, although it is understood that its multifunctional dysfunction involving many signaling pathways. This review summarized the common deterioration of signaling pathways and mechanisms involved in DN pathogenesis.

Research progress of TLRs signaling pathway in pathogenesis of dry eye

Research progress of TLRs signaling pathway in pathogenesis of dry eye

S1P Signaling Pathways in Pathogenesis of Type 2 Diabetes.

The pathogenesis of type 2 diabetes mellitus (T2DM) is very complicated. The currently well-accepted etiology is the “Ominous Octet” theory proposed by Professor Defronzo. Since presently used drugs for T2DM have limitations and harmful side effects, studies regarding alternative treatments are being conducted. Analyzing the pharmacological mechanism of biomolecules in view of pathogenesis is an effective way to assess new drugs. Sphingosine 1 phosphate (S1P), an endogenous lipid substance in the human body, has attracted increasing attention in the T2DM research field. This article reviews recent study updates of S1P, summarizing its effects on T2DM with respect to pathogenesis, promoting β cell proliferation and inhibiting apoptosis, reducing insulin resistance, protecting the liver and pancreas from lipotoxic damage, improving intestinal incretin effects, lowering basal glucagon levels, etc. With increasing research, S1P may help treat and prevent T2DM in the future.

Immunohistochemical analysis of beta-catenin expression: a probable prognostic marker and potential therapeutic target in renal cell carcinoma

Background and aimsRenal cell carcinoma (RCC) seems to be the most aggressive type of genitourinary neoplasm. Down regulation of normal beta-catenin expression contributes to development of RCC, reflecting the role of beta-catenin/Wnt signaling pathway in pathogenesis. This study aims to evaluate the significance of beta-catenin expression and its correlation with the prognostic parameters.MethodsA cross-sectional observational study was carried out in a tertiary care center on 58 RCC cases using variables like histological grade and type, tumor stage, necrosis. Formalin fixed, paraffin-embedded blocks were evaluated for beta-catenin expression by immunohistochemistry using scoring system. Data were analyzed by mean ± SD, χ2 test, Pearson’s correlation test.ResultsMembranous score (MS) had a strong negative correlation with tumor stage (r=−0.407, p=0.044) and grade (r=−0.787, p=<0.001). Mean membranous score difference between low (Stage 1 and 2) vs. high stage (Stage 3 and 4) and low (Grade 1 and 2) vs. high grade (Grade 3 and 4) was statistically significant (p<0.001). Cytoplasmic score (CS) had positive correlation with tumor stage (r=0.586; p=0.002). No significant correlation was evident between cytoplasmic scores and tumor grade, however the mean cytoplasmic score difference between low grade vs. high grade was statistically significant (p < 0.001).ConclusionBeta-catenin may play a crucial role in the pathogenesis of RCC and has a positive correlation with the biological behavior of this tumor. The important role of beta-catenin as a prognostic parameter and probably a critical evaluator of targeted chemotherapy cannot be overemphasized.

Role of Tenascin-X in regulating TGF-β/Smad signaling pathway in pathogenesis of slow transit constipation.

BACKGROUNDChronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients. Its incidence rate is 2%-27%. Slow transit constipation (STC) is a common type of chronic functional constipation, accounting for 10.3%-45.5% of such cases. Scholars have performed many studies on the pathogenesis of STC. These studies have indicated that the occurrence of STC may be related to multiple factors, such as dysfunction of the enteric nervous system, interstitial cells of Cajal (ICC) damage, and changes in neurotransmitters regulating intestinal peristalsis.AIMTo investigate the role of Tenascin-X (TNX) in regulating the TGF-β/Smad signaling pathway in the pathogenesis of STC.METHODSThis study included an experimental group and a control group. The experimental group included 28 patients with severe colonic STC, and the control group included 18 patients with normal colon tissues. Immunohistochemistry (IHC) was used to detect c-Kit, a specific marker of the ICC. Western blot, immunofluorescence, and IHC were used to detect the localization and expression of TNX and TGF-β/Smad.RESULTSIHC showed that the number of ICC with positive c-Kit expression was significantly reduced in the colon of STC patients (22.17 ± 3.28 vs 28.69 ± 3.53, P < 0.05) and that the distribution was abnormal. Western blot results showed that c-Kit and Smad7 levels were significantly decreased in the colon of STC patients (c-kit: 0.462 ± 0.099 vs 0.783 ± 0.178, P < 0.01; Smad7: 0.626 ± 0.058 vs 0.799 ± 0.03, P < 0.01) and that TNX and Smad2/3 levels were higher in the STC group (TNX: 0.868 ± 0.028 vs 0.482 ± 0.032, P < 0.01). There was no significant difference in TGF-β between the two groups (0.476 ± 0.028 vs 0.511 ± 0.044, P = 0.272). Pearson correlation analysis showed that the TNX protein exhibited a strong correlation with Smad2/3 and Smad7 (P < 0.05, |R| > 0.8) and TGF-β (P < 0.05, |R| = 0.7).CONCLUSIONThe extracellular matrix protein TNX may activate the TGF-β/Smad signaling pathway by upregulating the Smad 2/3 signaling protein and thereby induce slight or complete epithelial stromal cell transformation, leading to an abnormal distribution and dysfunction of ICC in the diseased colon, which promotes the occurrence and development of STC.

MicroRNA-15a - cell division cycle 42 signaling pathway in pathogenesis of pediatric inflammatory bowel disease.

AIMTo determine whether cell division cycle (Cdc)42 is regulated by microRNA (miR)-15a in the development of pediatric inflammatory bowel disease (IBD).METHODSWe cultured 293T cells, used plasmids and performed dual-luciferase assay to determine whether Cdc42 is a miR-15a target gene. We cultured Caco-2 cells, and stimulated them with tumor necrosis factor (TNF)-α. We then employed lentiviruses to alter the expression of miR-15a and Cdc42. We performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence to determine whether Cdc42 is regulated by miR-15a in Caco-2 cells. Finally, we collected ileocecal tissue by endoscopy from patients and performed qRT-PCR to examine the expression of miR-15a and Cdc42 in pediatric IBD patients.RESULTSTarget Scan and dual-luciferase assay revealed that Cdc42 was a miR-15a target gene. MiR-15a expression increased (P = 0.0038) and Cdc42 expression decreased (P = 0.0013) in cells stimulated with TNF-α, and the expression of the epithelial junction proteins zona occludens (ZO)-1 (P < 0.05) and E-cadherin (P < 0.001) decreased. Cdc42 levels decreased in miR-15a-mimic cells (P < 0.001) and increased in miR-15a inhibitor cells (P < 0.05). ZO-1 and E-cadherin decreased in miR-15a-mimic cells (P < 0.001) but not in the miR-15a inhibitor + TNF-α cells. In Lv-Cdc42 + TNF-α cells, ZO-1 and E-cadherin expression increased compared to the Lv-Cdc42-NC + TNF-α (P < 0.05) or miR-15a-mimic cells (P < 0.05). Fifty-four pediatric IBD patients were included in this study, 21 in the control group, 19 in the Crohn’s disease (CD) active (AC) group, seven in the CD remission (RE) group, and seven in the ulcerative colitis (UC) group. MiR-15a increased and Cdc42 decreased in the CD AC group compared to the control group (P < 0.05). miR-15a decreased and Cdc42 increased in the CD RE group compared to the CD AC group (P < 0.05). miR-15a was positively correlated with the Pediatric Crohn’s disease Activity Index (PCDAI) (P = 0.006), while Cdc42 was negatively correlated with PCDAI (P = 0.0008). Finally, miR-15a expression negatively correlated with Cdc42 in pediatric IBD patients (P = 0.0045).CONCLUSIONMiR-15a negatively regulates epithelial junctions through Cdc42 in Caco-2 cells and pediatric IBD patients.

Alterations in WNT Signaling in Leukemias.

The WNT/β-catenin signaling pathway plays an important role in the differentiation and proliferation of hematopoietic cells. In recent years, special attention has been paid to the role of impairments in the WNT signaling pathway in pathogenesis of malignant neoplasms of the hematopoietic system. Disorders in the WNT/β-catenin signaling in leukemias identified to date include hypersensitivity to the WNT ligands, epigenetic repression of WNT antagonists, overexpression of WNT ligands, impaired β-catenin degradation in the cytoplasm, and changes in the activity of the TCF/Lef transcription factors. At the molecular level, these impairments involve overexpression of the FZD protein, hypermethylation of the SFRP, DKK, WiF, Sox, and CXXC gene promoters, overexpression of Lef1 and plakoglobin, mutations in GSK3β, and β-catenin phosphorylation by the BCR-ABL kinase. This review is devoted to the systematization of these data.

Research advances in the role of the Hippo signaling pathway in pathogenesis of liver cancer

The Hippo signaling pathway consists of four core components in mammals, i.e., Mst1/2, WW45, Mob1, and LATS1/2, which can inhibit the transcriptional coactivator YAP from entering the nucleus, maintain the balance between cell proliferation and apoptosis, control organ size, and maintain homeostasis. If the core components of the Hippo signaling pathway are inactivated due to gene mutation or epigenetic alterations, YAP is overexpressed and activated in the nucleus, which then induces excessive cell proliferation and inhibits cell apoptosis. It has been confirmed that this process is closely associated with the formation of various tumors including liver cancer. Research on the Hippo signaling pathway may provide new directions for exploring the pathogenesis of liver tumor and developing effective therapies.

Restoration of miR-30a expression inhibits growth, tumorigenicity of medulloblastoma cells accompanied by autophagy inhibition

Medulloblastoma is a highly malignant pediatric brain tumor. About 30% patients have metastasis at diagnosis and respond poorly to treatment. Those that survive, suffer long term neurocognitive, endocrine and developmental defects due to the cytotoxic treatment to developing child brain. It is therefore necessary to develop targeted treatment strategies based on underlying biology for effective treatment of medulloblastoma with minimal side effects. Medulloblastomas are believed to be the result of deregulated nervous system development as evident from the role of WNT and SHH developmental signaling pathways in pathogenesis of medulloblastomas. MicroRNAs are known to play vital roles in nervous system development as well as in cancer. MicroRNA profiling of medulloblastomas identified miR-30 family members' expression to be downregulated in medulloblastomas belonging to the four known molecular subgroups viz. WNT, SHH, Group 3 and Group 4 as compared to that in normal brain tissues. Furthermore, established medulloblastoma cell lines Daoy, D283 and D425 were also found to underexpress miR-30a. Restoration of miR-30a expression using inducible lentiviral vector inhibited proliferation, clonogenic potential and tumorigenicity of medulloblastoma cells. MiR-30a is known to target Beclin1, a mediator of autophagy. MiR-30a expression was found to downregulate Beclin1 expression and inhibit autophagy in the medulloblastoma cell lines as judged by downregulation of LC3B expression and its turnover upon chloroquine treatment and starvation induced autophagy induction. MiR-30a therefore could serve as a novel therapeutic agent for the effective treatment of medulloblastoma by inhibiting autophagy that is known to play important role in cancer cell growth, survival and malignant behavior.

G-protein-coupled receptor signaling and neural tube closure defects.

Disruption of the normal mechanisms that mediate neural tube closure can result in neural tube defects (NTDs) with devastating consequences in affected patients. With the advent of next-generation sequencing, we are increasingly detecting mutations in multiple genes in NTD cases. However, our ability to determine which of these genes contribute to the malformation is limited by our understanding of the pathways controlling neural tube closure. G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in humans and have been historically favored as drug targets. Recent studies implicate several GPCRs and downstream signaling pathways in neural tube development and closure. In this review, we will discuss our current understanding of GPCR signaling pathways in pathogenesis of NTDs. Notable examples include the orphan primary cilia-localized GPCR, Gpr161 that regulates the basal suppression machinery of sonic hedgehog pathway by means of activation of cAMP-protein kinase A signaling in the neural tube, and protease-activated receptors that are activated by a local network of membrane-tethered proteases during neural tube closure involving the surface ectoderm. Understanding the role of these GPCR-regulated pathways in neural tube development and closure is essential toward identification of underlying genetic causes to prevent NTDs. Birth Defects Research 109:129-139, 2017. © 2016 Wiley Periodicals, Inc.

Role of phosphoinositide-3 kinase signaling pathways in pathogenesis of acute pancreatitis

Role of phosphoinositide-3 kinase signaling pathways in pathogenesis of acute pancreatitis

Roles of TGF-β/Smad signaling pathway in pathogenesis and development of gluteal muscle contracture

Purpose of the study: Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles which is characterized by excessive deposition of collagen in the extracellular matrix. Transforming growth factor (TGF)-βs have been shown to play an important role in the progression of GMC. However, the underlying mechanisms are not entirely clear. We sought to explore the expression of TGF-β/Smad pathway proteins and their downstream targets in gluteal muscle contracture disease.Materials and methods: The expression levels of collagens type I/III, TGF-β1, Smad2/3/4/7 and PAI-1 (plasminogen activator inhibitor type 1) in gluteal muscle contraction (GMC) patients were measured using immunohistochemistry, reverse transcription and polymerase chain reaction (RT-PCR) and western blot assays.Results: The expressions of collagens type I/III and TGF-β1 were significantly increased in the contraction band compared with unaffected muscle. In addition, R-Smad phosphorylation and Smad4 protein expression in the contraction band were also elevated, while the expression of Smad7 was significantly decreased in the fibrotic muscle of the GMC patients compared to the unaffected adjacent muscle. The protein and mRNA levels of PAI-1 were also remarkably increased in the contraction band compared with adjacent muscle. Immunohistochemical analysis also demonstrated that the expression levels of TGF-β1 and PAI-1 were higher in contraction band than those in the adjacent muscle.Conclusion: Our data confirm the stimulating effects of the TGF-β/Smad pathway in gluteal muscle contracture disease and reveal the internal changes of TGF-β/Smad pathway proteins and their corresponding targets in gluteal muscle contracture patients.

Role of NLRP3 and NLRP1 inflammasomes signaling pathways in pathogenesis of rheumatoid arthritis

ObjectivesTo investigate the role of NLRP3 and NLRP1 inflammasomes signaling pathways in rheumatoid arthritis (RA). MethodsA total of 36 patients with RA were selected, peripheral blood mononuclear cell (PBMC) and granulocyte were separated from venous blood. RT-qPCR method was used to detect the expression level and diversity of NLRP3 and NLRP1 in PBMC and granulocyte mRNA in patients with RA, and detect the mRNA expression of downstream factor IL-1α. The correlation between RA and the expression of NLRP3 and NLRP1 was analyzed. Normal 30 cases were set as control group. ResultsExpression levels of NLRP1, and caspase-1 mRNA in PBMC of RA group were significantly lower than those of control group (P<0.05), while there was no significant difference in expression levels of NLRP3, ASC, IL-1α mRNA between these two groups (P>0.05); NLRP3, caspase-1, and ASC mRNA expression in granulocyte of RA patients were significantly lower than those in control group (P<0.05). There was no correlation between rheumatoid factor and expression levels of NLRP3, ASC, caspase-1 mRNA in RA group (P>0.05); NLRP1, IL-1α mRNA expression level had a negative correlation with anti-rheumatoid factor antibody (P=0.033 2, 0.034 0). ConclusionsNLRP3 and NLRP1 inflammasomes signaling pathways are involved in RA inflammatory reaction process as protective factors, and play an important role in RA inflammatory mechanisms.

AMPK-NF-κB axis in the photoreceptor disorder during retinal inflammation.

Recent progress in molecular analysis has revealed the possible involvement of multiple inflammatory signaling pathways in pathogenesis of retinal degeneration. However, how aberrant signaling pathways cause tissue damage and dysfunction is still being elucidated. Here, we focus on 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), originally recognized as a key regulator of energy homeostasis. AMPK is also modulated in response to inflammatory signals, although its functions in inflamed tissue are obscure. We investigated the role of activated AMPK in the retinal neural damage and visual function impairment caused by inflammation. For this purpose, we used a mouse model of lipopolysaccharide-induced inflammation in the retina, and examined the effects of an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). During inflammation, activated AMPK in the neural retina was decreased, but AICAR treatment prevented this change. Moreover, the electroretinogram (ERG) a-wave response, representing photoreceptor function, showed visual dysfunction in this model that was prevented by AICAR. Consistently, the model showed shortened photoreceptor outer segments (OSs) with reduced levels of rhodopsin, a visual pigment concentrated in the OSs, in a post-transcriptional manner, and these effects were also prevented by AICAR. In parallel, the level of activated NF-κB increased in the retina during inflammation, and this increase was suppressed by AICAR. Treatment with an NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) preserved the rhodopsin level during inflammation, suppressing NF-κB. These findings indicated that AMPK activation by AICAR and subsequent NF-κB inhibition had a protective effect on visual function, and that AMPK activation played a neuroprotective role during retinal inflammation.