CircRNA HLCS regulates lens epithelial cell apoptosis via miR-338-3p/BPNT1 axis.

PURPOSE: The purpose of this study was to investigate the effect of circ_HLCS on age-related cataract (ARC). METHODS: Circ_HLCS, microRNA (miR)-338-3p, and bisphosphate 3'-nucleotidase 1 (BPNT1) were quantified by quantitative real-time polymerase chain reaction or western blot. Cell proliferation and cell viability were assessed by the 5-Ethynyl-2'-deoxyuridinr and cell counting kit-8 assays. Cell apoptosis was detected by flow cytometry. Targeted correlations among circ_HLCS, miR-338-3p, and BPNT1 were verified by the dual-luciferase reporter and RNA pull-down assays. RESULTS: circ_HLCS was diminished in ARC tissues and UV-treated SRA01/04 cells. Elevated content of circ_HLCS undermined UV-induced cell proliferation inhibition and apoptosis. Mechanistically, circ_HLCS directly targeted miR-338-3p, and circ_HLCS regulated BPNT1 expression through miR-338-3p. Furthermore, reduction of miR-338-3p ameliorated UV-induced SRA01/04 cell damage by increasing BPNT1 expression. CONCLUSION: Taken together, these data suggested that circ_HLCS inhibited apoptosis of UV-treated SRA01/04 cells by miR-338-3p/BPNT1 axis. Therefore, circ_HLCS might be a potential therapeutic target for ARC.

The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis.

INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.

Palmitic acid promotes human retinal pigment epithelial cells migration by upregulating miR-222 expression and inhibiting NUMB.

High glucose promotes retinal pigment epithelial cell (RPEC) migration. However, the underlying molecular mechanisms explaining how high fatty acid levels affect RPEC migration remain largely unknown. We investigated whether and how palmitic acid (PA) impacts the migration of human RPEC cell line ARPE-19. ARPE-19 cells were treated with varying doses of palmitic acid, and the RPEC migration was evaluated by scratch and transwell migration assays. Cell viability was determined by the CCK-8 method. The levels of epithelial-mesenchymal transition (EMT)-associated proteins, including E-cadherin, vimentin, MMP2, and MMP3, were evaluated by western blot. The microRNAs and mRNAs levels were assessed by quantitative PCR. miRNA targets were predicted with online tools and validated with the luciferase reporter assay. miRNA mimics, inhibitors, and siRNA oligos were used to perform gain-of-function and loss-of-function studies. We found that PA increased viability of ARPE-19 cells, promoted their migration and EMT. PA decreased E-cadherin protein expression, and increased vimentin, MMP2, and MMP3 protein levels. Additionally, PA increased miR-222 expression in ARPE-19 cells, and functionally blocking miR-222 suppressed the PA-induced RPEC migration and EMT. NUMB was identified as a downstream target of miR-222, and NUMB knockdown abolished the effects of PA on promoting the migration and EMT of ARPE-19 cells. Therefore, PA promotes human RPEC migration by upregulating miR-222 expression and downregulating NUMB. This study unravels a novel PA-miR-222-NUMB axis that can be potentially targeted for therapy of high fat acid-related ocular diseases.

Amphiphysin-IgG autoimmune sciatic neuropathy and facial neuropathy related to primary central nervous system lymphoma: A case report.

We reported a 61-year-old man presented with 10-month progressing left sciatic neuropathy and 10-day right facial neuropathy. Serum amphiphysin-IgG was positive. 18F-FDG PET/CT of the whole body showed no signs of malignancy. Treatment with plasma exchange and oral prednisone relieved the symptoms. Nine months later, right hemiparesis and seizure of right limbs developed. 18F-FDG and 18F-PBR06 (18 kDa translocator protein, TSPO) radioligand PET/MRI of the whole body revealed intense uptake in the intracranial lesions. Intracranial lymphoma was diagnosed by stereotactic needle brain biopsy. Mononeuropathies could be paraneoplastic syndromes. TSPO shows high uptake in intracranial lymphoma on 18F-PBR06 PET images.

A novel classification model based on cerebral 18F-FDG uptake pattern facilitates the diagnosis of acute/subacute seropositive autoimmune encephalitis.

PURPOSE: To explore the intrinsic alteration of cerebral 18F-FDG metabolism in acute/subacute seropositive autoimmune encephalitis (AE) and to propose a universal classification model based on 18F-FDG metabolic patterns to predict AE. METHODS: Cerebral 18F-FDG PET images of 42 acute/subacute seropositive AE patients and 45 healthy controls (HCs) were compared using voxelwise and region of interest (ROI)-based schemes. The mean standardized uptake value ratios (SUVRs) of 59 subregions according to a modified Automated Anatomical Labeling (AAL) atlas were compared using a t-test. Subjects were randomly divided into a training set (70%) and a testing set (30%). Logistic regression models were built based on the SUVRs and the models were evaluated by determining their predictive value in the training and testing sets. RESULTS: The 18F-FDG uptake pattern in the AE group was characterized by increased SUVRs in the brainstem, cerebellum, basal ganglia, and temporal lobe, and decreased SUVRs in the occipital, and frontal regions with voxelwise analysis (false discovery rate [FDR] p<0.05). Utilizing ROI-based analysis, we identified 15 subareas that exhibited statistically significant changes in SUVRs among AE patients compared to HC (FDR p<0.05). Further, a logistic regression model incorporating SUVRs from the calcarine cortex, putamen, supramarginal gyrus, cerebelum_10, and hippocampus successfully enhanced the positive predictive value from 0.76 to 0.86 when compared to visual assessments. This model also demonstrated potent predictive ability, with AUC values of 0.94 and 0.91 observed for the training and testing sets, respectively. CONCLUSIONS: During the acute/subacute stages of seropositive AE, alterations in SUVRs appear to be concentrated within physiologically significant regions, ultimately defining the general cerebral metabolic pattern. By incorporating these key regions into a new classification model, we have improved the overall diagnostic efficiency of AE.

Palmitic acid-induced microRNA-143-5p expression promotes the epithelial-mesenchymal transition of retinal pigment epithelium via negatively regulating JDP2.

BACKGROUND: The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is the most crucial step in the etiopathogenesis of proliferative vitreoretinopathy. This study aimed to investigate the role of miR-143-5p in the EMT of RPE cells induced by palmitic acid (PA). METHODS: ARPE-19 cells were treated with PA to induce EMT, followed by E-cadherin and α-smooth muscle actin (α-SMA) expression and the microRNA expression profile analyses. Subsequently, miR-143-5p mimics/inhibitors, and plasmids expressing its predicted target gene c-JUN-dimerization protein 2 (JDP2), were transfected in ARPE-19 cells using lipofectamine 3000, and followed by PA treatment. Their impacts on EMT were explored using wound healing and Western blot assays. Additionally, miR-143-5p mimics and JDP2-expressing plasmid were co-transfected into ARPE-19 cells and treated with PA to explore whether PA induced EMT of ARPE-19 cells via the miR-143-5p/JDP2 axis. RESULTS: PA decreased E-cadherin expression and increased those of α-SMA and miR-143-5p. Inhibiting miR-143-5p suppressed the migration of ARPE-19 cells and altered the expressions of E-cadherin and α-SMA. However, additional PA treatment attenuated these alterations. JDP2 was a target of miR-143-5p. Overexpression of JDP2 inhibited the EMT of ARPE-19 cells, resulting in α-SMA downregulation and E-cadherin upregulation, which were reversed by additional PA treatment via inhibiting JDP2 expression. Overexpression of miR-143-5p reversed the effect of JDP2 on the EMT of ARPE-19 cells and additional PA treatment markedly enhanced the effect of miR-143-5p mimics. CONCLUSION: PA promotes EMT of ARPE-19 cells via regulating the miR-143-5p/JDP2 axis, and these findings provide significant insights into the potential targeting of this axis to treat proliferative vitreoretinopathy.

Imaging of microglia in post-stroke inflammation.

Microglia constantly survey the central nervous system microenvironment and maintain brain homeostasis. Microglia activation, polarization and inflammatory response are of great importance in the pathophysiology of ischemic stroke. For exploring biochemical processes in vivo, positron emission tomography (PET) is a superior imaging tool. Translocator protein 18 kDa (TSPO), is a validated neuroinflammatory biomarker which is widely used to evaluate various central nervous system (CNS) pathologies in both preclinical and clinical studies. TSPO level can be elevated due to peripheral inflammatory cells infiltration and glial cells activation. Therefore, a clear understanding of the dynamic changes between microglia and TSPO is critical for interpreting PET studies and understanding the pathophysiology after ischemic stroke. Our review discusses alternative biological targets that have attracted considerable interest for the imaging of microglia activation in recent years, and the potential value of imaging of microglia in the assessment of stroke therapies.

Hypometabolism of the left middle/medial frontal lobe on FDG-PET in anti-NMDA receptor encephalitis: Comparison with MRI and EEG findings.

OBJECTIVES: To investigate changes in brain-glucose metabolism in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, and compare results with MRI and electroencephalography (EEG) findings at different disease stages. METHODS: The clinical data of 18 patients (median age, 35 years; 11 men) were retrospectively collected. Patients were divided into groups based on the time of symptom onset to examination, (≤1 month, >1 but ≤3 months, >3 months). Two-sample t-test results were compared with age and sex-paired healthy controls using statistical parametric mapping and verified using a NeuroQ software normal database with a discriminating z-score of 2. RESULTS: Abnormal patterns on FDG-PET differed over time (T = 3.21-8.74, Z = 2.68-4.23, p < 0.005). Regional analysis showed hypometabolic left middle or medial frontal cortex in 4/5, 5/7, and 5/6 patients, respectively. Time-subgroup analysis revealed hypermetabolic supertemporal cortex in 4/5, 5/7, and 2/6, patients, respectively. MRI and EEG abnormalities in any region and stage occurred in 10/18 and 10/16 patients, respectively. MRI and EEG time-subgroup analysis showed abnormalities in 5/9, 4/5, and 1/4, and 1/3, 6/7, and 3/6 patients, respectively. Abnormal temporal lobes were detected most frequently in MRI analyses and occurred in 3/10 patients. CONCLUSIONS: Decreased left middle/medial frontal metabolism could be common to all stages. Metabolism in other regions, MRI, and EEG results were associated with the progression of anti-NMDAR encephalitis. The sensitivity rate of FDG-PET was superior to that of MRI and EEG.

ß-asarone attenuates the proliferation, migration and enhances apoptosis of retinoblastoma through Wnt/ß-catenin signaling pathway.

PURPOSE: ß-asarone is the prime component of essential oil extracted from Acori graminei Rhizoma, which plays an inhibitory role in various tumors. Here, we aim to investigate the functions as well as the mechanism of ß-asarone in retinoblastoma (RB). METHODS: RB cell lines SO-Rb50 and HXO-Rb44 were treated with different doses of ß-asarone. Then, CCK8 and BrdU experiments were adopted to examine the RB cell proliferation. Wound healing test and Transwell assay were employed to detect cell migration and invasion. RB cell apoptosis was tested by flow cytometry and Western blot. An RB cell xenograft model was constructed on nude mice for testing the role of ß-asarone on RB cell growth in vivo. RT-PCR and Western blot were used to determine the effect of ß-asarone on Wnt/ß-catenin signaling pathway. Furthermore, the Wnt/ß-catenin pathway inhibitor PNU-74654 and activator HLY78 were administered to RB cells for confirming the effects of ß-asarone in Wnt/ß-catenin pathway. RESULTS: In vivo experiment showed that ß-asarone attenuated SO-Rb50 cell growth in nude mice. Further research found that ß-asarone significantly repressed Wnt/ß-catenin canonical pathway activation. CONCLUSION: Prior inhibition of Wnt/ß-catenin pathway abolished the antitumor effects induced by ß-asarone. ß-asarone exerted antitumor effects in RB cells by inactivating the Wnt/ß-catenin signaling pathway.

Enlarged perivascular spaces, neuroinflammation and neurological dysfunction in NMOSD patients.

Background and objectives: Cerebrospinal fluid (CSF) and interstitial fluid exchange along a brain-wide network of perivascular spaces (PVS) termed the 'glymphatic system'. The aquaporin-4 (AQP4) water channels abundantly expressed on astrocytic endfeet play a key role in the CSF circulation in the glymphatic system. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) featured with a specific autoantibody directed against AQP4 in most of patients. Anti-AQP4 antibodies are likely resulting in the impairment of the brain glymphatic system and the enlargement of PVS in NMOSD patients. In the current study, we aimed to demonstrate the features of EPVS detected by MRI and its association with the CSF anti-AQP4 antibody titer, CNS inflammatory markers, and disease severity in NMOSD patients. Methods: We conducted a retrospective review of a consecutive cohort of 110 patients with NMOSD who had brain MRI. We assessed the correlation of EPVS with markers of neuroinflammation, blood-brain barrier (BBB) function and severity of neurological dysfunction in patients. We used multivariate logistic regression analysis to determine the independent variables associated with disease severity. Results: The median number of total-EPVS was 15.5 (IQR, 11-24.2) in NMOSD patients. The number of total-EPVS was significantly related to EDSS score after correcting for the effects of age and hypertension (r=0.353, p<0.001). The number of total-EPVS was also significantly associated with the titer of CSF anti-AQP4 antibody, the albumin rate (CSF/serum ratios of albumin), the CSF albumin, IgG and IgA levels. Logistic regression analysis showed that total-EPVS and serum albumin level were two independent factors to predict disease severity in NMOSD patients (OR=1.053, p=0.028; OR=0.858, p=0.009 respectively). Furthermore, ROC analysis achieved AUC of 0.736 (0.640-0.831, p<0.001) for total-EPVS to determine severe NMOSD (EDSS 4.5-9.5). Discussion: In our cohort, we found a relationship between EPVS and neuroinflammation and BBB function in NMOSD. Moreover, EPVS might independently predict neurological dysfunction in patients with NMOSD.

Fatty acids role in multiple sclerosis as "metabokines".

Multiple sclerosis (MS), as an autoimmune neurological disease with both genetic and environmental contribution, still lacks effective treatment options among progressive patients, highlighting the need to re-evaluate disease innate properties in search for novel therapeutic targets. Fatty acids (FA) and MS bear an interesting intimate connection. FA and FA metabolism are highly associated with autoimmunity, as the diet-derived circulatory and tissue-resident FAs level and composition can modulate immune cells polarization, differentiation and function, suggesting their broad regulatory role as "metabokines". In addition, FAs are indeed protective factors for blood-brain barrier integrity, crucial contributors of central nervous system (CNS) chronic inflammation and progressive degeneration, as well as important materials for remyelination. The remaining area of ambiguity requires further exploration into this arena to validate the existed phenomenon, develop novel therapies, and confirm the safety and efficacy of therapeutic intervention targeting FA metabolism.

Cerebral Metabolic Network in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis on 18F-FDG PET Imaging.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis (AE), and the prognosis may significantly be improved if identified earlier and immune-related treated more effectively. This study evaluated the brain metabolic network using fluorodeoxyglucose positron emission tomography (FDG PET). Material and methods: FDG PET imaging of patients with NMDAR encephalitis was used to investigate the metabolic connectivity network, which was analyzed using the graph theory. The results in patients were compared to those in age- and sex-matched healthy controls. Results: The hub nodes were mainly in the right frontal lobe in patients with NMDAR encephalitis. The global and local efficiencies in most brain regions were significantly reduced, and the shortest characteristic path length was significantly longer, especially in the temporal and occipital lobes. Significant network functions of topology properties were enhanced in the right frontal, caudate nucleus, and cingulate gyrus. In addition, the internal connection integration in the left cerebral hemisphere was poor, and the transmission efficiency of Internet information was low. Conclusion: The present findings indicate that those characteristic and connections of metabolic network were changed in the brain by graph theory analysis quantitatively, which is helpful to better understand neuropathological and physiological mechanisms in patients with anti-NMDAR encephalitis.

Loss of serine/threonine protein kinase 25 in retinal ganglion cells ameliorates high glucose-elicited damage through regulation of the AKT-GSK-3ß/Nrf2 pathway.

Serine/threonine protein kinase 25 (STK25) has critical importance for diabetic complications. However, whether STK25 has a link with diabetic retinopathy is not clearly understood. The damages of retinal ganglion cells (RGCs) caused by high glucose (HG) is a critical determinant for the onset of diabetic retinopathy. Herein, this work focused on assessing the possible role of STK25 in HG-evoked damage to RGCs. An expression abundance of STK25 was occurred in RGCs challenged with HG. STK25 loss lowered the deleterious effects on RGCs, including apoptosis, oxidative stress and inflammation. SKT25 silencing strengthened the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway in HG-challenged RGCs. Moreover, the inhibition of STK25 restored the phosphorylation of AKT and glycogen synthase kinase-3ß (GSK-3ß) in HG-challenged RGCs, whereas limiting AKT decreased the motivating effects of STK25 inhibition on the Nrf2 pathway. Additionally, the beneficial effects of STK25 inhibition on HG injuries were also reversed via the inhibition of Nrf2. Based on these observations, our work suggests that the inhibition of STK25 is protective for RGCs suffering HG injuries, which is achieved by effects on the AKT-GSK-3ß/Nrf2 pathway. STK25 may participate in the onset of diabetic retinopathy by affecting HG-evoked damages of RGCs.

Proteinase-activated Receptor-1 Antagonist Attenuates Brain Injury via Regulation of FGL2 and TLR4 after Intracerebral Hemorrhage in Mice.

Proteinase-activated receptor-1 (PAR1) antagonist plays a protective effect in brain injury. We investigated the potential function and mechanisms of PAR1 antagonist in ICH-induced brain injury. Results showed that PAR1 antagonist protected against neurobehavior deficits, brain edema and blood-brain barrier integrity in ICH mice via the JNK/ERK/p38 MAPK signaling pathway at 24 h after ICH. In addition, ICH resulted in the increase of FGL2 and TLR4 expression over time, and phosphorylated (p-) JNK, ERK, p38 MAPK and IKKα expression. Suppression of FGL2 or TLR4 alleviated brain injury and decreased the expression of p-JNK, p-ERK, p-p38 MAPK and p-IKKα at 24 h after ICH, while overexpression of them showed the opposite result. Moreover, the protective effect of PAR1 antagonist on ICH-induced brain injury was blocked by FGL2 or TLR4 overexpression, and the levels of p-JNK, p-ERK and p-p38 MAPK were increased. Furthermore, PAR1 antagonist combined with TLR4 antagonist markedly alleviated brain injury after ICH at 72 h. Overall, PAR1 antagonist protected against short-term brain injury, and the effect of PAR1 antagonist on ICH-induced brain injury was mediated by FGL2 or TLR4.

Distinct roles of right temporoparietal cortex in pentagon copying test.

Pentagon Copying Test (PCT) is commonly used to assess visuospatial deficits, but the neural substrates underlying pentagon copying are not well understood. The Qualitative Scoring Pentagon Test (QSPT), an optimized scoring system, classifies five categories of errors patients make in pentagons copying and grades them depending on the errors' severity. To determine the strategic brain regions involved in the PCT, we applied the QSPT system to evaluate the visuospatial impairment of 136 acute ischemic stroke patients on the PCT and used Support Vector Regression Lesion-Symptom Mapping to investigate relevant brain regions. The total QSPT score was correlated with the right supramarginal gyrus. The angle number errors and closure errors were principally associated with lesions of the posterior temporoparietal cortex, including the right middle occipital gyrus and middle temporal gyrus, while the intersection errors and rotation errors were related to the more anterior part of the right temporoparietal lobe with the additional frontal cortex. In conclusion, the right temporoparietal cortex is the strategic region for pentagon copying tasks. The angle number and closure represent the visuospatial processing of within-object features, while intersection and rotation require between-object manipulation. The posterior-anterior distinction in the right temporoparietal region underlies the differences of within-object and between-object processing.

The Visuospatial and Sensorimotor Functions of Posterior Parietal Cortex in Drawing Tasks: A Review.

Drawing is a comprehensive skill that primarily involves visuospatial processing, eye-hand coordination, and other higher-order cognitive functions. Various drawing tasks are widely used to assess brain function. The neuropsychological basis of drawing is extremely sophisticated. Previous work has addressed the critical role of the posterior parietal cortex (PPC) in drawing, but the specific functions of the PPC in drawing remain unclear. Functional magnetic resonance imaging and electrophysiological studies found that drawing activates the PPC. Lesion-symptom mapping studies have shown an association between PPC injury and drawing deficits in patients with global and focal cerebral pathology. These findings depicted a core framework of the fronto-parietal network in drawing tasks. Here, we review neuroimaging and electrophysiological studies applying drawing paradigms and discuss the specific functions of the PPC in visuospatial and sensorimotor aspects. Ultimately, we proposed a hypothetical model based on the dorsal stream. It demonstrates the organization of a PPC-centered network for drawing and provides systematic insights into drawing for future neuropsychological research.

A PIK3R2 Mutation in Familial Temporal Lobe Epilepsy as a Possible Pathogenic Variant.

Temporal lobe epilepsy (TLE), the most common form of medically refractory focal epilepsy in adults, often requires surgery to alleviate seizures. By using next-generation sequencing, we identified a PIK3R2 mutation (NM_005027.4: c.265C > T; NP_005018.2: p.Arg89Cys) in a family with mesial temporal lobe epilepsy. PIK3R2 encodes p85ß, the regulatory subunit of Class IA phosphoinositide 3-kinase (PI3K) and the mutation we identified in PIK3R2 seems to function unexpectedly as a possible pathogenic variant. The mutation is predicted to be potentially pathogenic by multiple bioinformatics tools. Through a functional assay, we verified that the mutation enhances the function of PI3K in induced pluripotent stem cells (iPSCs) derived from peripheral blood mononuclear cells (PBMCs) of the proband. Finally, pathological testing of the resected temporal lobe cortex showed that the expression of PIK3R2 was significantly higher in patients with refractory temporal lobe epilepsy than in those of non-epileptic diseases as a control group. It can be inferred that PIK3R2 might play an important role in the development of TLE.

Modified cerebral small vessel disease score is associated with vascular cognitive impairment after lacunar stroke.

We conducted a cross-sectional study to characterize the relationship between total and modified small vessel disease (SVD) score with vascular cognitive impairment (VCI). Patients (n = 157) between the ages of 50 and 85 years old who had suffered their first lacunar infarction were analyzed prospectively. Brain magnetic resonance imaging was performed to identify SVD manifestations, which were used to calculate total or modified SVD scores. Neuropsychological assessments measured cognitive function. Spearman correlation analysis demonstrated that the total and modified SVD scores were associated with overall cognition as well as with function in the executive and visuospatial domains. The associations remained significant in linear regression after adjusting for age, sex, education and vascular risk factors. Binary logistic regression and chi-squared trend tests revealed that VCI risk increased significantly with SVD burden based on the modified SVD score. Subsequent chi-squared testing demonstrated that the VCI rate was significantly higher in patients with a modified SVD score of 5-6 than in patients without any SVD burden. Our results suggest that both the total and modified SVD scores show a negative association with cognitive function, but the modified SVD score may be better at identifying patients at high VCI risk.

TRIM27-mediated ubiquitination of PPARγ promotes glutamate-induced cell apoptosis and inflammation.

Neurotoxicity induced by glutamate (Glu) is often used to study the signaling mechanism of neurological disorders. The identification of specific genetic factors that cause Glu-induced neurotoxicity provides evidence for the common pathways of neuronal apoptosis and inflammation. TRIM27 has been found to induce apoptosis and inflammation. Nevertheless, there is little evidence that TRIM27 is associated with Glu-induced neurotoxicity. We found that TRIM27 expression was increased in epilepsy patients and in HT22 cells following Glu treatment. Glu-mediated cell apoptosis, decreased PPARγ expression, and increased levels of cleaved Caspase-3 and IL-1ß expression in HT22 cells were significantly inhibited by TRIM27 knockdown. TRIM27 overexpression significantly induced cell apoptosis and expression of cleaved Caspase-3 and IL-1ß, but inhibited PPARγ expression in HT22 cells, which were reversed by ROZ, suggesting the involvement of PPARγ in TRIM27-mediated cell apoptosis and inflammation in HT22 cells. Mechanically, TRIM27 ubiquitinates and degrades PPARγ, following induces cleaved Caspase-3 and IL-1ß expression. Clinically, increased expression of TRIM27 in epilepsy patients was associated with decreased PPARγ expression. Taken together, our study suggests that TRIM27-mediated ubiquitination of PPARγ promotes Glu-induced HT22 cell apoptosis and IL-1ß release.