NeuroMolecular Medicine最新文献_第3页

FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury. FMOD通过靶向创伤性脑损伤后的PI3K/AKT/mTOR信号传导缓解抑郁行为

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-06-12 DOI: 10.1007/s12017-024-08793-2

Xuekang Huang, Ziyu Zhu, Mengran Du, Chenrui Wu, Jiayuanyuan Fu, Jie Zhang, Weilin Tan, Biying Wu, Lian Liu, Z B Liao

{"title":"FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury.","authors":"Xuekang Huang, Ziyu Zhu, Mengran Du, Chenrui Wu, Jiayuanyuan Fu, Jie Zhang, Weilin Tan, Biying Wu, Lian Liu, Z B Liao","doi":"10.1007/s12017-024-08793-2","DOIUrl":"10.1007/s12017-024-08793-2","url":null,"abstract":"Depression frequently occurs following traumatic brain injury (TBI). However, the role of Fibromodulin (FMOD) in TBI-related depression is not yet clear. Previous studies have suggested FMOD as a potential key factor in TBI, yet its association with depression post-TBI and underlying mechanisms are not well understood. Serum levels of FMOD were measured in patients with traumatic brain injury using qPCR. The severity of depression was assessed using the self-depression scale (SDS). Neurological function, depressive state, and cognitive function in mice were assessed using the modified Neurological Severity Score (mNSS), forced swimming test (FST), tail suspension test (TST), Sucrose Preference Test (SPT), and morris water maze (MWM). The morphological features of mouse hippocampal synapses and neuronal dendritic spines were revealed through immunofluorescence, transmission electron microscopy, and Golgi-Cox staining. The protein expression levels of FMOD, MAP2, SYP, and PSD95, as well as the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway, were detected through Western blotting. FMOD levels were decreased in TBI patients' serum. Overexpression of FMOD preserved neuronal function and alleviated depression-like behaviour, increased synaptic protein expression, and induced ultrastructural changes in hippocampal neurons. The increased phosphorylation of PI3K, AKT, and mTOR suggested the involvement of the PI3K/AKT/mTOR signaling pathway in FMOD's protective effects. FMOD exhibits potential as a therapeutic target for depression related to TBI, with its protective effects potentially mediated through the PI3K/AKT/mTOR signaling pathway.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein Disulfide Isomerase Endoplasmic Reticulum Protein 57 (ERp57) is Protective Against ALS-Associated Mutant TDP-43 in Neuronal Cells. 蛋白二硫化物同工酶内质网蛋白 57 (ERp57) 对神经元细胞中与 ALS 相关的突变 TDP-43 有保护作用。

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-06-11 DOI: 10.1007/s12017-024-08787-0

Sonam Parakh, Emma R Perri, Marta Vidal, Zeinab Takalloo, Cyril J Jagaraj, Prachi Mehta, Shu Yang, Colleen J Thomas, Ian P Blair, Yuning Hong, Julie D Atkin

{"title":"Protein Disulfide Isomerase Endoplasmic Reticulum Protein 57 (ERp57) is Protective Against ALS-Associated Mutant TDP-43 in Neuronal Cells.","authors":"Sonam Parakh, Emma R Perri, Marta Vidal, Zeinab Takalloo, Cyril J Jagaraj, Prachi Mehta, Shu Yang, Colleen J Thomas, Ian P Blair, Yuning Hong, Julie D Atkin","doi":"10.1007/s12017-024-08787-0","DOIUrl":"10.1007/s12017-024-08787-0","url":null,"abstract":"Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease affecting motor neurons. Pathological forms of Tar-DNA binding protein-43 (TDP-43), involving its mislocalisation to the cytoplasm and the formation of misfolded inclusions, are present in almost all ALS cases (97%), and ~ 50% cases of the related condition, frontotemporal dementia (FTD), highlighting its importance in neurodegeneration. Previous studies have shown that endoplasmic reticulum protein 57 (ERp57), a member of the protein disulphide isomerase (PDI) family of redox chaperones, is protective against ALS-linked mutant superoxide dismutase (SOD1) in neuronal cells and transgenic SOD1G93A mouse models. However, it remains unclear whether ERp57 is protective against pathological TDP-43 in ALS. Here, we demonstrate that ERp57 is protective against key features of TDP-43 pathology in neuronal cells. ERp57 inhibited the mislocalisation of TDP-43M337V from the nucleus to the cytoplasm. In addition, ERp57 inhibited the number of inclusions formed by ALS-associated variant TDP-43M337V and reduced the size of these inclusions. ERp57 was also protective against ER stress and induction of apoptosis. Furthermore, ERp57 modulated the steady-state expression levels of TDP-43. This study therefore demonstrates a novel mechanism of action of ERp57 in ALS. It also implies that ERp57 may have potential as a novel therapeutic target to prevent the TDP-43 pathology associated with neurodegeneration.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

p39 Affects Myelin Formation in Cerebral Ischemic Injury. p39 影响脑缺血损伤中髓鞘的形成

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-06-01 DOI: 10.1007/s12017-024-08792-3

Danyang Meng, Di Wu, Xiaojing Li, Zhigang Miao

引用次数: 0

Influence of SLC40A1 on Cytokine Interactions and Immune Infiltration in Glioblastoma. SLC40A1 对胶质母细胞瘤中细胞因子相互作用和免疫渗透的影响

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-05-16 DOI: 10.1007/s12017-024-08789-y

Jiahao Jiang, Riquan Duan, Junle Zhu, Junqing Yan, Jingliang Ye, Chun Luo

{"title":"Influence of SLC40A1 on Cytokine Interactions and Immune Infiltration in Glioblastoma.","authors":"Jiahao Jiang, Riquan Duan, Junle Zhu, Junqing Yan, Jingliang Ye, Chun Luo","doi":"10.1007/s12017-024-08789-y","DOIUrl":"10.1007/s12017-024-08789-y","url":null,"abstract":"Numerous studies have explored the various functions of Slc40a1 in cancer development. However, the role of Slc40a1 in primary glioblastoma requires further investigation. Initially, we observed that GBM patients with high Slc40a1 expression had a more favorable prognosis than those with low Slc40a1 expression, as evidenced by an analysis of the TIMER database. Subsequent analysis using the cancer genome atlas (TCGA) database enabled us to identify potential underlying mechanisms involved. Further analyses, including GO, KEGG, GSEA, immune infiltration, and correlation analyses, revealed that Slc40a1 primarily affected cytokine interactions, particularly with Ccl14 and Il18, resulting in changes in the immune microenvironment and ultimately leading to a better prognosis in GBM patients. We validated our findings by examining a tissue microarray with 180 samples and confirmed that GBM patients with high SLC40A1 protein expression exhibited more favorable prognostic outcomes than those with low SLC40A1 protein expression. Immunofluorescence analysis also revealed a significant correlation between SLC40A1 protein expression and the protein expression of IL18 and CCL14. These findings suggest that Slc40a1 may play a role in GBM pathogenesis by modulating the tumor immune microenvironment through the regulation of Il18 and Ccl14. Hence, targeting Slc40a1 might offer potential benefits for immunotherapeutic interventions and prognostic assessments in GBM patients.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder. 揭开内源性大麻素系统的神秘面纱：探索自闭症谱系障碍的治疗潜力。

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-05-14 DOI: 10.1007/s12017-024-08781-6

Ankit Jana, Arnab Nath, Palash Sen, Swikriti Kundu, Badrah S Alghamdi, Turki S Abujamel, Muhammad Saboor, Chan Woon-Khiong, Athanasios Alexiou, Marios Papadakis, Mohammad Zubair Alam, Ghulam Md Ashraf

{"title":"Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder.","authors":"Ankit Jana, Arnab Nath, Palash Sen, Swikriti Kundu, Badrah S Alghamdi, Turki S Abujamel, Muhammad Saboor, Chan Woon-Khiong, Athanasios Alexiou, Marios Papadakis, Mohammad Zubair Alam, Ghulam Md Ashraf","doi":"10.1007/s12017-024-08781-6","DOIUrl":"10.1007/s12017-024-08781-6","url":null,"abstract":"The salient features of autism spectrum disorder (ASD) encompass persistent difficulties in social communication, as well as the presence of restricted and repetitive facets of behavior, hobbies, or pursuits, which are often accompanied with cognitive limitations. Over the past few decades, a sizable number of studies have been conducted to enhance our understanding of the pathophysiology of ASD. Preclinical rat models have proven to be extremely valuable in simulating and analyzing the roles of a wide range of established environmental and genetic factors. Recent research has also demonstrated the significant involvement of the endocannabinoid system (ECS) in the pathogenesis of several neuropsychiatric diseases, including ASD. In fact, the ECS has the potential to regulate a multitude of metabolic and cellular pathways associated with autism, including the immune system. Moreover, the ECS has emerged as a promising target for intervention with high predictive validity. Particularly noteworthy are resent preclinical studies in rodents, which describe the onset of ASD-like symptoms after various genetic or pharmacological interventions targeting the ECS, providing encouraging evidence for further exploration in this area.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Clemizole on Alpha-Synuclein-Preformed Fibrils-Induced Parkinson's Disease Pathology: A Pharmacological Investigation. 氯咪唑对α-突触核蛋白纤维诱发帕金森病病理的影响：药理学研究

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-05-04 DOI: 10.1007/s12017-024-08785-2

Bhupesh Vaidya, Pankaj Gupta, Soumojit Biswas, Joydev K Laha, Ipsita Roy, Shyam Sunder Sharma

{"title":"Effect of Clemizole on Alpha-Synuclein-Preformed Fibrils-Induced Parkinson's Disease Pathology: A Pharmacological Investigation.","authors":"Bhupesh Vaidya, Pankaj Gupta, Soumojit Biswas, Joydev K Laha, Ipsita Roy, Shyam Sunder Sharma","doi":"10.1007/s12017-024-08785-2","DOIUrl":"https://doi.org/10.1007/s12017-024-08785-2","url":null,"abstract":"Parkinson's disease (PD) is a neurodegenerative disorder associated with mitochondrial dysfunctions and oxidative stress. However, to date, therapeutics targeting these pathological events have not managed to translate from bench to bedside for clinical use. One of the major reasons for the lack of translational success has been the use of classical model systems that do not replicate the disease pathology and progression with the same degree of robustness. Therefore, we employed a more physiologically relevant model involving alpha-synuclein-preformed fibrils (PFF) exposure to SH-SY5Y cells and Sprague Dawley rats. We further explored the possible involvement of transient receptor potential canonical 5 (TRPC5) channels in PD-like pathology induced by these alpha-synuclein-preformed fibrils with emphasis on amelioration of oxidative stress and mitochondrial health. We observed that alpha-synuclein PFF exposure produced neurobehavioural deficits that were positively ameliorated after treatment with the TRPC5 inhibitor clemizole. Furthermore, Clemizole also reduced p-alpha-synuclein and diminished oxidative stress levels which resulted in overall improvements in mitochondrial biogenesis and functions. Finally, the results of the pharmacological modulation were further validated using siRNA-mediated knockdown of TRPC5 channels, which also decreased p-alpha-synuclein expression. Together, the results of this study could be superimposed in the future for exploring the beneficial effects of TRPC5 channel modulation for other neurodegenerative disorders and synucleopathies.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Seipin Deficiency Leads to Energy Dyshomeostasis via Inducing Hypothalamic Neuroinflammation and Aberrant Expression of Neuropeptides 塞品基因缺陷通过诱导下丘脑神经炎症和神经肽的异常表达导致能量失衡

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-05-01 DOI: 10.1007/s12017-024-08788-z

Wenli Cui, Hong Chen, Lingfeng Lei, Wenru Wang, Kah-Leong Lim, Chengwu Zhang, Li Lu

引用次数: 0

Long-Term Accumulation of T Cytotoxic 1, T Cytotoxic 17, and T Cytotoxic 17/1 Cells in the Brain Contributes to Microglia-Mediated Chronic Neuroinflammation After Ischemic Stroke 脑内T细胞毒性1、T细胞毒性17和T细胞毒性17/1细胞的长期积累是缺血性脑卒中后小胶质细胞介导的慢性神经炎症的原因之一

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-04-29 DOI: 10.1007/s12017-024-08786-1

Long Shu, Hui Xu, Jiale Ji, Yuhan Xu, Ziyue Dong, Yuchen Wu, Yijing Guo

{"title":"Long-Term Accumulation of T Cytotoxic 1, T Cytotoxic 17, and T Cytotoxic 17/1 Cells in the Brain Contributes to Microglia-Mediated Chronic Neuroinflammation After Ischemic Stroke","authors":"Long Shu, Hui Xu, Jiale Ji, Yuhan Xu, Ziyue Dong, Yuchen Wu, Yijing Guo","doi":"10.1007/s12017-024-08786-1","DOIUrl":"https://doi.org/10.1007/s12017-024-08786-1","url":null,"abstract":"Post-stroke neuroinflammation affects the damage and recovery of neurological functions. T cells including CD8+ T cells were present in the ipsilateral hemisphere in the subacute and late phases of ischemic stroke. However, the potential roles of CD8+ T cell subsets in the progression of neuroinflammation have not been characterized. In the current mouse transient middle cerebral artery occlusion model, we investigated the existence of CD8+ T cell subsets in the ipsilateral hemisphere in the subacute and late phases of stroke. We found that ipsilateral CD8+ T cells were present on post-stroke day 3 and increased on post-stroke day 30. The day-3 ipsilateral CD8+ T cells predominantly produced interferon-γ (IFN-γ), while the day-30 ipsilateral CD8+ T cells co-expressed IFN-γ and interleukin-17A (IL-17A). In addition, evaluation of cytokines and transcription factors of the day-30 ipsilateral CD8+ T cells revealed the presence of T cytotoxic 1 (Tc1), T cytotoxic 17 (Tc17), and T cytotoxic 17/1 (Tc17/1) cells. Furthermore, based on the expression of a series of chemokine/cytokine receptors, viable ipsilateral Tc1, Tc17, and Tc17.1 cells were identified and enriched from the day-30 ipsilateral CD8+ T cells, respectively. Co-culture of microglia with ipsilateral Tc1, Tc17, or Tc17.1 cells indicated that the three CD8+ T cell subsets up-regulated the expression of pro-inflammatory mediators by microglia, with Tc17.1 cells being the most potent cell in doing so. Collectively, this study sheds light on the contributions of Tc1, Tc17, and Tc17.1 cells to long-term neuroinflammation after ischemic stroke.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140833342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Resiquimod Induces C-C Motif Chemokine Ligand 2 Via Nuclear Factor-Kappa B in SH-SY5Y Human Neuroblastoma Cells Resiquimod 通过核因子-Kappa B 在 SH-SY5Y 人神经母细胞瘤细胞中诱导 C-C Motif 趋化因子配体 2

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-04-26 DOI: 10.1007/s12017-024-08782-5

Masatoshi Kaizuka, S. Kawaguchi, Tetsuya Tatsuta, Mayuki Tachizaki, Yuri Kobori, Yusuke Tanaka, K. Seya, T. Matsumiya, Tadaatsu Imaizumi, H. Sakuraba

引用次数: 0

Lycium Barbarum Polysaccharides Improves Cognitive Functions in ICV-STZ-Induced Alzheimer’s Disease Mice Model by Improving the Synaptic Structural Plasticity and Regulating IRS1/PI3K/AKT Signaling Pathway 枸杞多糖通过改善突触结构可塑性和调节 IRS1/PI3K/AKT 信号通路改善 ICV-STZ 诱导的阿尔茨海默病模型小鼠的认知功能

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-04-23 DOI: 10.1007/s12017-024-08784-3

Yingxi He, Yanyou Wang, Xia Li, Yanqiang Qi, Zuwei Qu, Yan-li Hu

引用次数: 0