Mia Langbøl, Arevak Saruhanian, Sarkis Saruhanian, Daniel Tiedemann, Thisayini Baskaran, Rupali Vohra, Amalie Santaolalla Rives, José Moreira, Verena Prokosch, Hanhan Liu, Jan-Wilm Lackmann, Stefan Müller, Claus Henrik Nielsen, Miriam Kolko, Jens Rovelt
{"title":"Proteomic and Cytokine Profiling in Plasma from Patients with Normal-Tension Glaucoma and Ocular Hypertension.","authors":"Mia Langbøl, Arevak Saruhanian, Sarkis Saruhanian, Daniel Tiedemann, Thisayini Baskaran, Rupali Vohra, Amalie Santaolalla Rives, José Moreira, Verena Prokosch, Hanhan Liu, Jan-Wilm Lackmann, Stefan Müller, Claus Henrik Nielsen, Miriam Kolko, Jens Rovelt","doi":"10.1007/s10571-024-01492-3","DOIUrl":"10.1007/s10571-024-01492-3","url":null,"abstract":"<p><p>Primary open-angle glaucoma (POAG) is subdivided depending on eye pressure. Patients with normal-tension glaucoma (NTG) have never had high intraocular pressure (IOP) measured while patients with ocular hypertension (OHT) have high eye pressure but no signs of glaucoma. Although IOP is considered to be a risk factor for all glaucoma patients, it is reasonable to assume that other risk factors such as inflammation play a role. We aimed to characterize the proteome and cytokine profile during hypoxia in plasma from patients with NTG (n = 10), OHT (n = 10), and controls (n = 10). Participants were exposed to hypoxia for two hours, followed by 30 min of normoxia. Samples were taken before (\"baseline\"), during (\"hypoxia\"), and after hypoxia (\"recovery\"). Proteomics based on liquid chromatography coupled with mass spectrometry (LC-MS) was performed. Cytokines were measured by Luminex assays. Bioinformatic analyses indicated the involvement of complement and coagulation cascades in NTG and OHT. Regulation of high-density lipoprotein 3 (HDL3) apolipoproteins suggested that changes in cholesterol metabolism are related to OHT. Hypoxia decreased the level of tumor necrosis factor-α (TNF-α) in OHT patients compared to controls. Circulating levels of interleukin-1β (IL-1β) and C-reactive protein (CRP) were decreased in NTG patients compared to controls during hypoxia. After recovery, plasma interleukin-6 (IL-6) was upregulated in patients with NTG and OHT. Current results indicate an enhanced systemic immune response in patients with NTG and OHT, which correlates with pathogenic events in glaucoma. Apolipoproteins may have anti-inflammatory effects, enabling OHT patients to withstand inflammation and development of glaucoma despite high IOP.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"59"},"PeriodicalIF":3.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987486","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}
{"title":"Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review.","authors":"Chao Cui, Xue Jiang, Yumei Wang, Chao Li, Zhaochen Lin, Youzhen Wei, Qingbin Ni","doi":"10.1007/s10571-024-01491-4","DOIUrl":"10.1007/s10571-024-01491-4","url":null,"abstract":"<p><p>This article comprehensively reviews how cerebral hypoxia impacts the physiological state of neurons and dendritic spines through a series of molecular changes, and explores the causal relationship between these changes and neuronal functional impairment. As a severe pathological condition, cerebral hypoxia can significantly alter the morphology and function of neurons and dendritic spines. Specifically, dendritic spines, being the critical structures for neurons to receive information, undergo changes such as a reduction in number and morphological abnormalities under hypoxic conditions. These alterations further affect synaptic function, leading to neurotransmission disorders. This article delves into the roles of molecular pathways like MAPK, AMPA receptors, NMDA receptors, and BDNF in the hypoxia-induced changes in neurons and dendritic spines, and outlines current treatment strategies. Neurons are particularly sensitive to cerebral hypoxia, with their apical dendrites being vulnerable to damage, thereby affecting cognitive function. Additionally, astrocytes and microglia play an indispensable role in protecting neuronal and synaptic structures, regulating their normal functions, and contributing to the repair process following injury. These studies not only contribute to understanding the pathogenesis of related neurological diseases but also provide important insights for developing novel therapeutic strategies. Future research should further focus on the dynamic changes in neurons and dendritic spines under hypoxic conditions and their intrinsic connections with cognitive function.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"58"},"PeriodicalIF":3.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892932","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}
Qian Zhang, Tianjiao Li, Mengying Xu, Binish Islam, Jianwu Wang
{"title":"Application of Optogenetics in Neurodegenerative Diseases.","authors":"Qian Zhang, Tianjiao Li, Mengying Xu, Binish Islam, Jianwu Wang","doi":"10.1007/s10571-024-01486-1","DOIUrl":"10.1007/s10571-024-01486-1","url":null,"abstract":"<p><p>Optogenetics, a revolutionary technique integrating optical and genetic methodologies, offers unparalleled precision in spatial targeting and temporal resolution for cellular control. This approach enables the selective manipulation of specific neuronal populations, inducing subtle electrical changes that significantly impact complex neural circuitry. As optogenetics precisely targets and modulates neuronal activity, it holds the potential for significant breakthroughs in understanding and potentially altering the course of neurodegenerative diseases, characterized by selective neuronal loss leading to functional deficits within the nervous system. The integration of optogenetics into neurodegenerative disease research has significantly advanced in the field, offering new insights and paving the way for innovative treatment strategies. Its application in clinical settings, although still in the nascent stages, suggests a promising future for addressing some of the most challenging aspects of neurodegenerative disorders. In this review, we provide a comprehensive overview of these research undertakings.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"57"},"PeriodicalIF":3.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765631","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}
Naif H Ali, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Najah R Hadi, Abdullah A Assiri, Mohammed Alrouji, Nermeen N Welson, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha
{"title":"Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon.","authors":"Naif H Ali, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Najah R Hadi, Abdullah A Assiri, Mohammed Alrouji, Nermeen N Welson, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha","doi":"10.1007/s10571-024-01489-y","DOIUrl":"10.1007/s10571-024-01489-y","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory impairment and cognitive dysfunctions. It has been shown that hypoglycemia can adversely affect AD neuropathology. It is well-known that chronic hyperglycemia in type 2 diabetes (T2D) is regarded as a potential risk factor for the development and progression of AD. However, the effect of recurrent hypoglycemia on the pathogenesis of AD was not deeply discussed, and how recurrent hypoglycemia affects AD at cellular and molecular levels was not intensely interpreted by the previous studies. The underlying mechanisms for hypoglycaemia-induced AD are diverse such as endothelial dysfunction, thrombosis, and neuronal injury that causing tau protein hyperphosphorylation and the accumulation of amyloid beta (Aβ) in the brain neurons. Of note, the glucagon hormone, which controls blood glucose, can also regulate the cognitive functions. Glucagon increases blood glucose by antagonizing the metabolic effect of insulin. Therefore, glucagon, through attenuation of hypoglycemia, may prevent AD neuropathology. Glucagon/GLP-1 has been shown to promote synaptogenesis, hippocampal synaptic plasticity, and learning and memory, while attenuating amyloid and tau pathologies. Therefore, activation of glucagon receptors in the brain may reduce AD neuropathology. A recent glucagon receptor agonist dasiglucagon which used in the management of hypoglycemia may be effective in preventing hypoglycemia and AD neuropathology. This review aims to discuss the potential role of dasiglucagon in treating hypoglycemia in AD, and how this drug reduce AD neuropathology.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"55"},"PeriodicalIF":3.6,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558168","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}
Anna Di Vito, Annalidia Donato, Jessica Bria, Francesco Conforti, Domenico La Torre, Natalia Malara, Giuseppe Donato
{"title":"Extracellular Matrix Structure and Interaction with Immune Cells in Adult Astrocytic Tumors.","authors":"Anna Di Vito, Annalidia Donato, Jessica Bria, Francesco Conforti, Domenico La Torre, Natalia Malara, Giuseppe Donato","doi":"10.1007/s10571-024-01488-z","DOIUrl":"10.1007/s10571-024-01488-z","url":null,"abstract":"<p><p>The extracellular matrix (ECM) is a dynamic set of molecules produced by the cellular component of normal and pathological tissues of the embryo and adult. ECM acts as critical regulator in various biological processes such as differentiation, cell proliferation, angiogenesis, and immune control. The most frequent primary brain tumors are gliomas and by far the majority are adult astrocytic tumors (AATs). The prognosis for patients with these neoplasms is poor and the treatments modestly improves survival. In the literature, there is a fair number of studies concerning the composition of the ECM in AATs, while the number of studies relating the composition of the ECM with the immune regulation is smaller. Circulating ECM proteins have emerged as a promising biomarker that reflect the general immune landscape of tumor microenvironment and may represent a useful tool in assessing disease activity. Given the importance it can have for therapeutic and prognostic purposes, the aim of our study is to summarize the biological properties of ECM components and their effects on the tumor microenvironment and to provide an overview of the interactions between major ECM proteins and immune cells in AATs. As the field of immunotherapy in glioma is quickly expanding, we retain that current data together with future studies on ECM organization and functions in glioma will provide important insights into the tuning of immunotherapeutic approaches.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"54"},"PeriodicalIF":3.6,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537672","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}
{"title":"Therapeutic Implications and Regulations of Protein Post-translational Modifications in Parkinsons Disease.","authors":"Twinkle Mishra, Shareen Singh, Thakur Gurjeet Singh","doi":"10.1007/s10571-024-01471-8","DOIUrl":"10.1007/s10571-024-01471-8","url":null,"abstract":"<p><p>Parkinsons disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss and alpha-synuclein aggregation. This comprehensive review examines the intricate role of post-translational modifications (PTMs) in PD pathogenesis, focusing on DNA methylation, histone modifications, phosphorylation, SUMOylation, and ubiquitination. Targeted PTM modulation, particularly in key proteins like Parkin, DJ1, and PINK1, emerges as a promising therapeutic strategy for mitigating dopaminergic degeneration in PD. Dysregulated PTMs significantly contribute to the accumulation of toxic protein aggregates and dopaminergic neuronal dysfunction observed in PD. Targeting PTMs, including epigenetic strategies, addressing aberrant phosphorylation events, and modulating SUMOylation processes, provides potential avenues for intervention. The ubiquitin-proteasome system, governed by enzymes like Parkin and Nedd4, offers potential targets for clearing misfolded proteins and developing disease-modifying interventions. Compounds like ginkgolic acid, SUMO E1 enzyme inhibitors, and natural compounds like Indole-3-carbinol illustrate the feasibility of modulating PTMs for therapeutic purposes in PD. This review underscores the therapeutic potential of PTM-targeted interventions in modulating PD-related pathways, emphasizing the need for further research in this promising area of Parkinsons disease therapeutics.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"53"},"PeriodicalIF":3.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497248","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}
Sergio Davinelli, Alessandro Medoro, Rosa Savino, Giovanni Scapagnini
{"title":"Sleep and Oxidative Stress: Current Perspectives on the Role of NRF2.","authors":"Sergio Davinelli, Alessandro Medoro, Rosa Savino, Giovanni Scapagnini","doi":"10.1007/s10571-024-01487-0","DOIUrl":"10.1007/s10571-024-01487-0","url":null,"abstract":"<p><p>Sleep is a fundamental conserved physiological state across evolution, suggesting vital biological functions that are yet to be fully clarified. However, our understanding of the neural and molecular basis of sleep regulation has increased rapidly in recent years. Among various processes implicated in controlling sleep homeostasis, a bidirectional relationship between sleep and oxidative stress has recently emerged. One proposed function of sleep may be the mitigation of oxidative stress in both brain and peripheral tissues, contributing to the clearance of reactive species that accumulate during wakefulness. Conversely, reactive species, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), at physiological levels, may act as signaling agents to regulate redox-sensitive transcriptional factors, enzymes, and other effectors involved in the regulation of sleep. As a primary sensor of intracellular oxidation, the transcription factor NRF2 is emerging as an indispensable component to maintain cellular redox homeostasis during sleep. Indeed, a number of studies have revealed an association between NRF2 dysfunction and the most common sleep conditions, including sleep loss, obstructive sleep apnea, and circadian sleep disturbances. This review examines the evidence of the intricate link between oxidative stress and NRF2 function in the context of sleep, and highlights the potential of NRF2 modulators to alleviate sleep disturbances.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"52"},"PeriodicalIF":3.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445716","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}
Paula M Wagner, Santiago J Fornasier, Mario E Guido
{"title":"Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology.","authors":"Paula M Wagner, Santiago J Fornasier, Mario E Guido","doi":"10.1007/s10571-024-01485-2","DOIUrl":"10.1007/s10571-024-01485-2","url":null,"abstract":"<p><p>The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12-15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase 1 ε/δ (CK1ε/δ) with specific inhibitors (CHIR99021 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption after Per2 knockdown expression in GBM-derived cells. CHIR99021-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition compared to control cells. The combined treatment of CHIR99021 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone. Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects GBM cell biology.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"51"},"PeriodicalIF":3.6,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440208","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}
Shu-Han Zhao, Xin-Yu Ji, Guo-Zhen Yuan, Tao Cheng, Hai-Yi Liang, Si-Qi Liu, Fu-Yi Yang, Yang Tang, Shuai Shi
{"title":"A Bibliometric Analysis of the Spatial Transcriptomics Literature from 2006 to 2023.","authors":"Shu-Han Zhao, Xin-Yu Ji, Guo-Zhen Yuan, Tao Cheng, Hai-Yi Liang, Si-Qi Liu, Fu-Yi Yang, Yang Tang, Shuai Shi","doi":"10.1007/s10571-024-01484-3","DOIUrl":"10.1007/s10571-024-01484-3","url":null,"abstract":"<p><p>In recent years, spatial transcriptomics (ST) research has become a popular field of study and has shown great potential in medicine. However, there are few bibliometric analyses in this field. Thus, in this study, we aimed to find and analyze the frontiers and trends of this medical research field based on the available literature. A computerized search was applied to the WoSCC (Web of Science Core Collection) Database for literature published from 2006 to 2023. Complete records of all literature and cited references were extracted and screened. The bibliometric analysis and visualization were performed using CiteSpace, VOSviewer, Bibliometrix R Package software, and Scimago Graphica. A total of 1467 papers and reviews were included. The analysis revealed that the ST publication and citation results have shown a rapid upward trend over the last 3 years. Nature Communications and Nature were the most productive and most co-cited journals, respectively. In the comprehensive global collaborative network, the United States is the country with the most organizations and publications, followed closely by China and the United Kingdom. The author Joakim Lundeberg published the most cited paper, while Patrik L. Ståhl ranked first among co-cited authors. The hot topics in ST are tissue recognition, cancer, heterogeneity, immunotherapy, differentiation, and models. ST technologies have greatly contributed to in-depth research in medical fields such as oncology and neuroscience, opening up new possibilities for the diagnosis and treatment of diseases. Moreover, artificial intelligence and big data drive additional development in ST fields.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"44 1","pages":"50"},"PeriodicalIF":4.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295606","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}