Neutrophil extracellular traps in central nervous system (CNS) diseases.

Excessive induction of inflammatory and immune responses is widely considered as one of vital factors contributing to the pathogenesis and progression of central nervous system (CNS) diseases. Neutrophils are well-studied members of inflammatory and immune cell family, contributing to the innate and adaptive immunity. Neutrophil-released neutrophil extracellular traps (NETs) play an important role in the regulation of various kinds of diseases, including CNS diseases. In this review, current knowledge on the biological features of NETs will be introduced. In addition, the role of NETs in several popular and well-studied CNS diseases including cerebral stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and neurological cancers will be described and discussed through the reviewing of previous related studies.

Depletion of ß-arrestin-1 in macrophages enhances atherosclerosis in ApoE-/- mice.

Autophagy in atherosclerotic plaque macrophage contributes to the alleviation of atherosclerosis through the promotion of lipid metabolism. ß-arrestins are multifunctional proteins participating various kinds of cellular signaling pathways. Here we aimed to determine the role of ß-arrestin-1, an important member of ß-arrestin family, in atherosclerosis, and whether autophagy was involved in this process. ApoE-/-ß-arrestin-1fl/flLysM-Cre mice were created through bone marrow transplantation for the atherosclerosis model with conditional myeloid knocking out ß-arrestin-1. Bone marrow-derived macrophages (BMDMs) were used for the in vitro studies. Oil red O staining was used to detect the lesional area. F4/80, Masson trichrome and picro-Sirius red staining were applied for the determination of plaque stability. Real-time PCR was used for the detection of levels of lipid metabolism-related receptors. Electron microscopy and tandem fluorescent mRFP-GFP-LC3 plasmid was applied to test autophagy level. We found that ß-arrestin-1 was highly increased in expression in plaque macrophage on the occurrence of atherosclerosis. Conditional myeloid knocking out ß-arrestin-1 largely promotes plaque formation and vulnerability. In murine macrophage with lipid loading, knocking down ß-arrestin-1 enhanced foam cell formation and levels of plasma and cellular cholesterol, while overexpressing ß-arrestin-1 led to the opposite effects. The alleviative effects induced by macrophage ß-arrestin-1 in atherosclerosis were involved in autophagy, based on the reduction of autophagy level with the knocking down of macrophage ß-arrestin-1 and administration of autophagy inhibitors which largely attenuated the decreasing effect on foam cell formation. Our results demonstrated for the first time that macrophage ß-arrestin-1 protected against atherosclerosis through the induction of autophagy.

Repeat peroral endoscopic myotomy with simultaneous submucosal and muscle dissection as a salvage option for recurrent achalasia.

BACKGROUND: For recurrent achalasia after initial peroral endoscopic myotomy (POEM) failure, repeat POEM (Re-POEM) has been reported as a treatment option. However, severe esophageal interlayer adhesions caused by previous procedures impede the successful establishment of a submucosal tunnel and lead to aborted Re-POEM procedures. Our team previously described POEM with simultaneous submucosal and muscle dissection (POEM-SSMD) as a feasible solution for achalasia with severe interlayer adhesions. AIM: To investigate the effectiveness and safety of Re-POEM with simultaneous submucosal and muscle dissection (Re-POEM-SSMD). METHODS: A total of 1049 patients with achalasia who underwent successful endoscopic myotomy at the Digestive Endoscopic Center of Chinese PLA General Hospital from December 2014 to May 2022 were reviewed. Patients with recurrent achalasia who experienced initial POEM clinical failure were retrospectively included in this study. The primary endpoint was retreatment clinical success, defined as an Eckardt score ≤ 3 during the postretreatment follow-up and no need for additional treatment. Procedure-related adverse events, changes in manometric lower esophageal sphincter (LES) pressure and reflux complications, as well as procedure-related parameters, were recorded. RESULTS: Sixteen patients underwent Re-POEM (9 patients) or Re-POEM-SSMD (7 patients) successfully at a median of 45.5 mo (range, 4-95 mo) after initial POEM. During a median follow-up period of 31 mo (range, 7-96 mo), clinical success (Eckardt score ≤ 3) was achieved in 8 (88.9%) and 6 (85.7%) patients after Re-POEM and Re-POEM-SSMD, respectively (P = 0.849). The median Eckardt score dropped from 4 (range, 3-8) at preretreatment to 1 (range, 0-5) at postretreatment in the Re-POEM group (P = 0.025) and from 5 (range, 2-8) to 2 (range, 0-4) in the Re-POEM-SSMD group (P < 0.001). The mean manometric LES pressure decreased from 23.78 ± 9.04 mmHg to 11.45 ± 5.37 mmHg after Re-POEM (P < 0.001) and from 26.80 ± 7.48 mmHg to 11.05 ± 4.38 mmHg after Re-POEM-SSMD (P < 0.001). No serious adverse events were recorded in both groups. CONCLUSION: In conclusion, Re-POEM-SSMD appears to be a safe and effective salvage therapy for recurrent achalasia with severe interlayer adhesions.

Linked color imaging vs Lugol chromoendoscopy for esophageal squamous cell cancer and precancerous lesion screening: A noninferiority study.

BACKGROUND: Lugol chromoendoscopy (LCE) has served as a standard screening technique in high-risk patients with esophageal cancer. Nevertheless, LCE is not suitable for general population screening given its side effects. Linked color imaging (LCI) is a novel image-enhanced endoscopic technique that can distinguish subtle diff-erences in mucosal color. AIM: To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions. METHODS: In this prospective study, we enrolled 543 patients who underwent white light imaging (WLI), LCI and LCE successively. We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions. Clinicopathological features and color analysis of lesions were assessed. RESULTS: In total, 43 patients (45 neoplastic lesions) were analyzed. Among them, 36 patients (38 neoplastic lesions) were diagnosed with LCI, and 39 patients (41 neoplastic lesions) were diagnosed with LCE. The sensitivity of LCI was similar to that of LCE (83.7% vs 90.7%, P = 0.520), whereas the specificity of LCI was greater than that of LCE (92.4% vs 87.0%, P = 0.007). The LCI procedure time in the esophageal examination was significantly shorter than that of LCE [42 (34, 50) s vs 160 (130, 189) s, P < 0.001]. The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI. However, the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer. CONCLUSION: LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions, and LCI represents a promising screening strategy for general populations.

NLRP3 Inflammasome in Atherosclerosis: Putting Out the Fire of Inflammation.

Atherosclerosis (AS) is a chronic inflammatory disease with thickening or hardening of the arteries, which led to the built-up of plaques in the inner lining of an artery. Among all the clarified pathogenesis, the over-activation of inflammatory reaction is one of the most acknowledged one. The nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3 (NLRP3) inflammasome, as a vital and special form of inflammation and innate immunity, has been widely revealed to participate in the onset and development of AS. This review will introduce the process of the pathogenesis and progression of AS, and will describe the biological features of the NLRP3 inflammasome. Furthermore, the role of the NLRP3 inflammasome in AS and the possible mechanisms will be discussed. In addition, several kinds of agents with the effect of anti-atherosclerotic taking advantage of the NLRP3 inflammasome intervention will be described and discussed in detail, including natural compounds (baicalin, dihydromyricetin, luteolin, 5-deoxy-rutaecarpine (R3) and Salvianolic acid A, etc.), microRNAs (microRNA-30c-5p, microRNA-9, microRNA-146a-5p, microRNA-16-5p and microRNA-181a, etc.), and autophagy regulators (melatonin, dietary PUFA and arglabin, etc.). We aim to provide novel insights in the exploration of the specific mechanisms of AS and the development of new treatments of AS.

Autophagy in gastrointestinal cancers.

Gastrointestinal cancers are a group of cancers occurred in gastrointestinal tissues with high morbidity and mortality rate. Although numerous studies were conducted on the investigation of gastrointestinal cancers, the real mechanisms haven't been discovered, and no effective methods of prevention and treatment of gastrointestinal cancers have been developed. Autophagy, a vital catabolic process in organisms, have been proven to participate in various mechanisms and signaling pathways, thus producing a regulatory effect on various diseases. The role of autophagy in gastrointestinal cancers remains unclear due to its high complexity. In this review, firstly, the biological features of autophagy will be introduced. Secondly, the role of autophagy in three popular gastrointestinal cancers, namely esophageal cancer, gastric cancer, and colorectal cancer will be described and discussed by reviewing the related literature. We aimed to bring novel insights in exploring the real mechanisms for gastrointestinal cancers and developing effective and efficient therapeutic methods to treat gastrointestinal cancers.

Comparison between endoscopic submucosal tunnel dissection and endoscopic submucosal dissection for superficial neoplasia at esophagogastric junction: a case-matched controlled study of a single center from China.

BACKGROUND: So far, little evidence is available for the comprehensive comparison of endoscopic submucosal tunnel dissection (ESTD) with endoscopic submucosal dissection (ESD) for the treatment of superficial neoplasia at esophagogastric junction (EGJ). METHODS: EGJ superficial neoplasia patients with ESTD treatment between January, 2021 and August, 2020 were retrospectively reviewed and individually matched at 1:1 ratio with those with ESD treatment according to lesion size, specimen area and lesion location, forming ESTD and ESD group, respectively. A sample size of 17 patients was collected for each group. Treatment outcomes including resection time, specimen area, and resection speed as well as occurrence of complications were evaluated. RESULTS: Compared with ESD group, ESTD group got shorter resection time (111.00 ± 11.70 min for ESD group vs. 71.59 ± 6.18 min for ESTD group, p = 0.008) and faster section speed (0.23 ± 0.03 cm2/min for ESD group vs. 0.37 ± 0.06 cm2/min for ESTD group, p = 0.012). No complication was found to occur in ESTD group, while 1 patient with MP damage and 1 with delayed bleeding was found in ESD group. CONCLUSION: For the treatment of EGJ superficial neoplasia, ESTD is a safer and more effective and reliable endoscopic technique compared with ESD.

The Role of Neutrophil Extracellular Traps in Cancer.

Neutrophils are vital components of innate and adaptive immunity. It is widely acknowledged that in various pathological conditions, neutrophils are activated and release condensed DNA strands, triggering the formation of neutrophil extracellular traps (NETs). NETs have been shown to be effective in fighting against microbial infections and modulating the pathogenesis and progression of diseases, including malignant tumors. This review describes the current knowledge on the biological characteristics of NETs. Additionally, the mechanisms of NETs in cancer are discussed, including the involvement of signaling pathways and the crosstalk between other cancer-related mechanisms, including inflammasomes and autophagy. Finally, based on previous and current studies, the roles of NET formation and the potential therapeutic targets and strategies related to NETs in several well-studied types of cancers, including breast, lung, colorectal, pancreatic, blood, neurological, and cutaneous cancers, are separately reviewed and discussed.

The Role of Autophagy in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn's disease (CD). The abnormality of inflammatory and immune responses in the intestine contributes to the pathogenesis and progression of IBD. Autophagy is a vital catabolic process in cells. Recent studies report that autophagy is highly involved in various kinds of diseases, especially inflammation-related diseases, such as IBD. In this review, the biological characteristics of autophagy and its role in IBD will be described and discussed based on recent literature. In addition, several therapies for IBD through modulating the inflammasome and intestinal microbiota taking advantage of autophagy regulation will be introduced. We aim to bring new insight in the exploration of mechanisms for IBD and development of novel therapeutic strategies against IBD.

Intestinal autophagy links psychosocial stress with gut microbiota to promote inflammatory bowel disease.

Psychosocial stress is a critical inducing factor of inflammatory bowel diseases (IBD), while autophagy is a novel central issue of IBD development. The present study investigated the potential role of autophagy in stress-related IBD in patients and animal model. The correlation between psychosocial stress and intestinal autophagy was determined in 23 patients with IBD. Corticotropin-releasing hormone (CRH), a well-established inducer of psychosocial stress, was administrated in dextran sulfate sodium (DSS)-induced IBD mice and lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDM). In IBD patients, the autophagy markers beclin-1, LC3-II/I ratio, Atg16L1, and Atg4B were significantly enhanced. The psychosocial stress score was positively associated with the levels of beclin-1 and the LC3II/I ratio in intestinal biopsy specimens. In IBD mouse model, CRH significantly aggravated intestinal inflammation, increased Paneth cell metaplasia, and enhanced intestinal autophagy (beclin-1, Atg16L1, PIK3R4, and Atg4B upregulation; GAA, CTSD, and PPKAA1 downregulation). Additionally, the CRH-induced gut microbial dysbiosis was evidenced by a marked increase in the number of detrimental bacteria. In LPS-stimulated BMDM, CRH substantially increased M1/M2 polarization and thus promoted inflammation. In both IBD mice and LPS-treated BMDM, blockade of autophagy by chloroquine abrogated the unbeneficial effects of CRH, whereas autophagy inducer rapamycin resulted in a pronounced protective effect against IBD lesion. Our data demonstrate that psychosocial stress may link the enhanced intestinal autophagy by modulating gut microbiota and inflammation to aggravate IBD. These data indicate autophagy as a promising therapeutic target for psychosocial stress-related IBD.

Alpha7 Nicotinic Acetylcholine Receptor Alleviates Inflammatory Bowel Disease Through Induction of AMPK-mTOR-p70S6K-Mediated Autophagy.

Alpha7 nicotinic acetylcholine receptor (α7nAChR) has been reported to be protective in several kinds of disorders through inflammatory suppression. Here, we investigated the role of α7nAChR in inflammatory bowel disease (IBD) on α7nAChR deficient mice (α7nAChR-/-) and the wild-type mice (α7nAChR+/+). Three percent dextran sulfate sodium (DSS) was used for the creation of IBD mice model and lipopolysaccharides (LPS)/DSS as an inflammatory stressor in murine bone marrow-derived macrophages (BMDMs). The severity of IBD was determined and HE staining as well as enzyme-linked immunosorbent assay (ELISA) and real-time PCR were used to detect the level of inflammatory activation. Western blot was used to determine the levels of autophagy-related proteins. Transmission electron microscopy and mRFP-GFP-LC3 plasmid were applied to determine the levels of autophagy. We demonstrated that deficiency in α7nAChR produced a detrimental effect on IBD severity and inflammatory reaction in DSS-induced colitis models. Those effects were led to via autophagy dysfunction. α7nAChR deficiency attenuated the protective and anti-inflammatory effect of autophagy inducer in IBD mice and BMDMs challenged with LPS/DSS. The alleviative effect of activating α7nAChR was attenuated through inhibiting adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mediated signaling. In conclusion, α7nAChR contributes to alleviate IBD through the induction of AMPK-mammalian target of rapamycin rabbit (mTOR)-p70 ribosomal protein S6 kinase (p70S6K)-mediated autophagy, thus providing a novel target for the treatment of IBD.

Targeting NLRP3 Inflammasome in Inflammatory Bowel Disease: Putting out the Fire of Inflammation.

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, comprised of ulcerative colitis and Crohn's disease. Among the complicated pathogenic factors of IBD, the overaction of inflammatory and immune reaction serves as an important factor. Inflammasome is a form of innate immunity as well as inflammation. Among all kinds of inflammasomes, the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is the most studied one, and has been revealed to be involved in the pathogenesis and progression of IBD. Here, in this review, the association between the NLRP3 inflammasome and IBD will be discussed. Furthermore, several NLRP3 inflammasome inhibitors which have been demonstrated to be effective in the alleviation of IBD will be described in this review.

A Systematic Review of Neuroprotective Efficacy and Safety of DL-3-N-Butylphthalide in Ischemic Stroke.

DL-3-n-butylphthalide (NBP) is widely used as a neuroprotective drug for ischemic stroke in China. There is, however, no established evidence on its efficacy and safety for patients with ischemic stroke. We, therefore, conducted a systematic review and meta-analysis. Major databases were searched to identify randomized controlled trials that assessed the efficacy and safety of NBP on ischemic stroke, reporting outcomes among patients treated with NBP alone or combined with standard anti-ischemic stroke drugs vs. standard anti-ischemic stroke drugs. Continuous data were validated, extracted and synthesized of standardized mean differences (SMDs) by random effects models, while dichotomous data were validated, extracted and synthesized of relative risk (RR) by random effects models. Twelve randomized controlled trials involving 1160 patients were identified. Results suggested that NBP monotherapy is not superior to standard anti-ischemic stroke drugs based on the Barthel Index (SMD, 0.25; 95% CI - 0.14 to 0.63; P=0.21 ) and the National Institutes of Health Stroke Scale (SMD, 0.73; 95% CI - 0.14 to 1.59; P=0.10 ). In contrast, the combination of NBP and standard anti-ischemic stroke drugs appears to be superior to standard drugs alone, again based on both the Barthel index (SMD, 1.65; 95% CI 1.25 to 2.04; P<0.01 ) and National Institutes of Health Stroke Scale (SMD, 1.40; 95% CI 0.72 to 2.09; P<0.01 ). However, the use of NBP may cause adverse event on the function of the liver (RR, 3.55; 95% CI 1.19 to 10.56; P<0.05 ). The combination use of NBP and standard anti-ischemic stroke drugs is more effective than standard drugs. However, more attention should be payed to the adverse effects on liver function. Our findings provided an established evidence of NBP as a neuroprotective drug, which may improve the current guideline for treatment of ischemic stroke.

Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases.

Central nervous system (CNS) is one of the largest killers of people's health all over the world. The overactivation of the immune and inflammatory responses is considered as an important factor, contributing to the pathogenesis and progression of CNS disorders. Among all kinds of immune and inflammatory reaction, the inflammasome, a complex of proteins, has been drawn increasingly attention to by researchers. The initiation and activation of the inflammasome is involved in the onset of various kinds of diseases. The NLRP3 inflammasome, the most studied member of the inflammasome, is closely associated with many kinds of CNS disorders. Here in this review, the roles of the NLRP3 inflammasome in the pathogenesis and progression of several well-known CNS diseases would be discussed, including cerebrovascular diseases, neurodegenerative diseases, multiple sclerosis, depression as well as other CNS disorders. In addition, several therapeutic strategies targeting on the NLRP3 inflammasome for the treatment of CNS disorders would be described in this review.

Impact of Paneth Cell Autophagy on Inflammatory Bowel Disease.

Intestinal mucosal barrier, mainly consisting of the mucus layer and epithelium, functions in absorbing nutrition as well as prevention of the invasion of pathogenic microorganisms. Paneth cell, an important component of mucosal barrier, plays a vital role in maintaining the intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Current evidence shows that the dysfunction of intestinal mucosal barrier, especially Paneth cell, participates in the onset and progression of inflammatory bowel disease (IBD). Autophagy, a cellular stress response, involves various physiological processes, such as secretion of proteins, production of antimicrobial peptides, and degradation of aberrant organelles or proteins. In the recent years, the roles of autophagy in the pathogenesis of IBD have been increasingly studied. Here in this review, we mainly focus on describing the roles of Paneth cell autophagy in IBD as well as several popular autophagy-related genetic variants in Penath cell and the related therapeutic strategies against IBD.

Autophagy in ischemic stroke.

Autophagy is a self-eating cellular catabolic pathway, through which long-lived proteins, damaged organelles and misfolded proteins are degraded and recycled for the maintenance of cellular homeostasis and normal cellular functions. Autophagy plays an important homeostatic role in the regulation of cell survival. Accumulating evidence shows that autophagy is activated in various cell types in the brain such as neurons, glia cells, and brain microvascular cells upon ischemic stroke. However, the exact role and molecular mechanisms of autophagy process that is implicated in ischemic stroke have yet to be elucidated. This review aims to provide a comprehensive view of the regulation of autophagy in neurons, glia cells, and brain microvascular cells in response to ischemia stress. We also review the recent advance on the understanding of the involvement of autophagy in the pathological process during cerebral ischemic preconditioning, perconditioning and postconditioning. We propose a crosstalk between autophagy, necroptosis, and apoptosis that contribute to ischemic stroke. In addition, we discuss the interactions between autophagy and oxidative stress, mitochondrial dysfunction and endoplasmic reticulum stress.

Activating α7 nicotinic acetylcholine receptor inhibits NLRP3 inflammasome through regulation of ß-arrestin-1.

AIMS: To evaluate whether activating α7 nicotinic acetylcholine receptor (α7nAChR) could inhibit the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome through regulation of ß-arrestin-1 in monocyte/macrophage system, thus contributing to the control of neuroinflammation. METHODS: The protein levels of NLRP3, caspase-1 (Casp-1) p20 and proCasp-1, interleukin-1ß (IL-1ß) p17 and proIL-1ß, IL-18 and proIL-18 were measured using Western blotting. The mRNA levels of Casp-1 and IL-1ß were detected by real-time PCR (RT-PCR). The colocalization and interaction of NLRP3 protein and ß-arrestin-1 were measured by immunofluorescence staining and immunoprecipitation. RESULTS: The expression of ß-arrestin-1 was significantly increased and colocalized with CD45-positive cells in spinal cord of experimental auto-immune encephalomyelitis (EAE) mice when compared with the sham mice, which was attenuated by pretreatment with PNU282987, a specific α7nAChR agonist. PNU282987 also significantly inhibited the activation of NLRP3 inflammasome and thus decreased the production of IL-1ß and IL-18 both in lipopolysaccharide (LPS)/ATP-stimulated BV2 microglia in vitro and spinal cord from EAE mice in vivo, while inverse effects were observed in α7nAChR knockout mice. Furthermore, overexpression of ß-arrestin-1 attenuated the inhibitory effect of PNU282987 on NLRP3 inflammasome activation in LPS/ATP-stimulated BV2 microglia. PNU282987 inhibited the interaction between ß-arrestin-1 and NLRP3 protein in vitro. CONCLUSIONS: The present study demonstrates that activating α7nAChR can lead to NLRP3 inflammasome inhibition via regulation of ß-arrestin-1 in monocyte/microglia system.

Autophagy Plays an Important Role in Anti-inflammatory Mechanisms Stimulated by Alpha7 Nicotinic Acetylcholine Receptor.

Alpha7 nicotinic acetylcholine receptor (α7nAChR) has been reported to alleviate neuroinflammation. Here, we aimed to determine the role of autophagy in α7nAChR-mediated inhibition of neuroinflammation and its underlying mechanism. Experimental autoimmune encephalomyelitis (EAE) mice and lipopolysaccharide-stimulated BV2 microglia were used as in vivo and in vitro models of neuroinflammation, respectively. The severity of EAE was evaluated with neurological scoring. Autophagy-related proteins (Beclin 1, LC3-II/I, p62/SQSTM1) were detected by immunoblot. Autophagosomes were observed using transmission electron microscopy and tandem fluorescent mRFP-GFP-LC3 plasmid was applied to test autophagy flux. The mRNA levels of interleukin-6 (IL-6), IL-1ß, IL-18, and tumor necrosis factor-α (TNF-α) were detected by real-time PCR. We used 3-methyladenine (3-MA) and autophagy-related gene 5 small interfering RNA (Atg5 siRNA) to block autophagy in vivo and in vitro, respectively. Activating α7nAChR with PNU282987 ameliorates EAE severity and spinal inflammatory infiltration in EAE mice. PNU282987 treatment also enhanced monocyte/microglia autophagy (Beclin 1, LC3-II/I ratio, p62/SQSTM1, colocalization of CD45- or CD68-positive cells with LC3) both in spinal cord and spleen from EAE mice. The beneficial effects of PNU282987 on EAE mice were partly abolished by 3-MA, an autophagy inhibitor. In vitro, PNU282987 treatment increased autophagy and promoted autophagy flux. Blockade of autophagy by Atg5 siRNA or bafilomycin A1 attenuated the inhibitory effect of PNU282987 on IL-6, IL-1ß, IL-18, and TNF-α mRNA. Our results demonstrate for the first time that activating α7nAChR enhances monocyte/microglia autophagy, which suppresses neuroinflammation and thus plays an alleviative role in EAE.