Journal of Neuroinflammation最新文献

{"title":"Imaging the eye as a window to brain health: frontier approaches and future directions.","authors":"Hasan U Banna, Mary Slayo, James A Armitage, Blanca Del Rosal, Loretta Vocale, Sarah J Spencer","doi":"10.1186/s12974-024-03304-3","DOIUrl":"10.1186/s12974-024-03304-3","url":null,"abstract":"<p><p>Recent years have seen significant advances in diagnostic testing of central nervous system (CNS) function and disease. However, there remain challenges in developing a comprehensive suite of non- or minimally invasive assays of neural health and disease progression. Due to the direct connection with the CNS, structural changes in the neural retina, retinal vasculature and morphological changes in retinal immune cells can occur in parallel with disease conditions in the brain. The retina can also, uniquely, be assessed directly and non-invasively. For these reasons, the retina may prove to be an important \"window\" for revealing and understanding brain disease. In this review, we discuss the gross anatomy of the eye, focusing on the sensory and non-sensory cells of the retina, especially microglia, that lend themselves to diagnosing brain disease by imaging the retina. We include a history of ocular imaging to describe the different imaging approaches undertaken in the past and outline current and emerging technologies including retinal autofluorescence imaging, Raman spectroscopy, and artificial intelligence image analysis. These new technologies show promising potential for retinal imaging to be used as a tool for the diagnosis of brain disorders such as Alzheimer's disease and others and the assessment of treatment success.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"21 1","pages":"309"},"PeriodicalIF":9.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engrailed-2 and inflammation convergently and independently impinge on cerebellar Purkinje cell differentiation.","authors":"Mohammed Bahaaeldin, Carolin Bülte, Fabienne Luelsberg, Sujeet Kumar, Joachim Kappler, Christof Völker, Karl Schilling, Stephan L Baader","doi":"10.1186/s12974-024-03301-6","DOIUrl":"10.1186/s12974-024-03301-6","url":null,"abstract":"<p><p>Autism spectrum disorders (ASD) have a complex pathogenesis thought to include both genetic and extrinsic factors. Among the latter, inflammation of the developing brain has recently gained growing attention. However, how genetic predisposition and inflammation might converge to precipitate autistic behavior remains elusive. Cerebellar structure and function are well known to be affected in autism. We therefore used cerebellar slice cultures to probe whether inflammatory stimulation and (over)expression of the autism susceptibility gene Engrailed-2 interact in shaping differentiation of Purkinje cells, key organizers of cerebellar histogenesis and function. We show that lipopolysaccharide treatment reduces Purkinje cell dendritogenesis and that this effect is enhanced by over-expression of Engrailed-2 in these cells. The effects of lipopolysaccharide can be blocked by inhibiting microglia proliferation and also by blocking tumor necrosis factor alpha receptor signaling, suggesting microglia and tumor necrosis factor alpha are major players in this scenario. These findings identify Purkinje cells as a potential integrator of genetic and environmental signals that lead to an autism-associated morphology.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"21 1","pages":"306"},"PeriodicalIF":9.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taprenepag restores maternal-fetal interface homeostasis for the treatment of neurodevelopmental disorders.","authors":"Kai Wang, Shufen Zhang, Yunxia Wang, Xiaomei Wu, Lijuan Wen, Tingting Meng, Xiangyu Jin, Sufen Li, Yiling Hong, Jia Ke, Yichong Xu, Hong Yuan, Fuqiang Hu","doi":"10.1186/s12974-024-03300-7","DOIUrl":"10.1186/s12974-024-03300-7","url":null,"abstract":"<p><strong>Background and purpose: </strong>Neurodevelopmental disorders (NDDs) are characterized by abnormalities in brain development and neurobehaviors, including autism. The maternal-fetal interface (MFI) is a highly specialized tissue through which maternal factors affect fetal brain development. However, limited research exists on restoring and maintaining MFI homeostasis and its potential impact on NDDs. This study explores the role of placental indoleamine 2,3-dioxygenase (IDO-1) in MFI homeostasis and fetal brain development.</p><p><strong>Experimental approach: </strong>The maternal-fetal barrier was disrupted by sodium valproate (VPA) in pregnant mice, whose offspring show typical autism-like behaviors. Ultrastructural analysis and flow cytometric analysis were conducted to observe the morphological and immune system changes. Behavioral tests and immunofluorescence staining was used to investigate the ability and mechanism of taprenepag to alleviate the abnormal behaviors of VPA-exposed offspring and normalize the development of serotonergic neurons.</p><p><strong>Key results: </strong>In VPA-exposed pregnant mice, the downregulation of IDO-1 led to maternal immune overactivation and disruption of maternal-fetal barrier, resulting in excessive 5-HT synthesis in the placenta. This process disrupted the development of the serotonergic neuronal system in the offspring, resulting in impaired development of serotonergic neurons, thalamocortical axons, and NDDs in the progeny. However, a single injection of taprenepag at E13.5 ultimately upregulated placental IDO-1 through amplifying the positive feedback loop COX-2/PGE₂/PTGER-2/IDO-1 and abolished these alterations.</p><p><strong>Conclusion: </strong>Taprenepag improved autism-like behaviors in the offspring of VPA-exposed mice by addressing placental IDO-1 downregulation. This study highlights the potential of targeting IDO-1 to mitigate MFI disruption and NDD development.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"21 1","pages":"307"},"PeriodicalIF":9.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate metabolism and histone lactylation in the central nervous system disorders: impacts and molecular mechanisms.","authors":"Yao Wang, Ping Li, Yuan Xu, Linyu Feng, Yongkang Fang, Guini Song, Li Xu, Zhou Zhu, Wei Wang, Qi Mei, Minjie Xie","doi":"10.1186/s12974-024-03303-4","DOIUrl":"10.1186/s12974-024-03303-4","url":null,"abstract":"<p><p>Brain takes up approximately 20% of the total body oxygen and glucose consumption due to its relatively high energy demand. Glucose is one of the major sources to generate ATP, the process of which can be realized via glycolysis, oxidative phosphorylation, pentose phosphate pathways and others. Lactate serves as a hub molecule amid these metabolic pathways, as it may function as product of glycolysis, substrate of a variety of enzymes and signal molecule. Thus, the roles of lactate in central nervous system (CNS) diseases need to be comprehensively elucidated. Histone lactylation is a novel lactate-dependent epigenetic modification that plays an important role in immune regulation and maintaining homeostasis. However, there's still a lack of studies unveiling the functions of histone lactylation in the CNS. In this review, we first comprehensively reviewed the roles lactate plays in the CNS under both physiological and pathological conditions. Subsequently, we've further discussed the functions of histone lactylation in various neurological diseases. Furthermore, future perspectives regarding histone lactylation and its therapeutic potentials in stroke are also elucidated, which may possess potential clinical applications.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"21 1","pages":"308"},"PeriodicalIF":9.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR4-dependent neuroinflammation mediates LPS-driven food-reward alterations during high-fat exposure.","authors":"Sabrina J P Huwart, Clémence Fayt, Giuseppe Gangarossa, Serge Luquet, Patrice D Cani, Amandine Everard","doi":"10.1186/s12974-024-03297-z","DOIUrl":"10.1186/s12974-024-03297-z","url":null,"abstract":"<p><strong>Background: </strong>Obesity has become a global pandemic, marked by significant shifts in both the homeostatic and hedonic/reward aspects of food consumption. While the precise causes are still under investigation, recent studies have identified the role of gut microbes in dysregulating the reward system within the context of obesity. Unravelling these gut-brain connections is crucial for developing effective interventions against eating and metabolic disorders, particularly in the context of obesity. This study explores the causal role of LPS, as a key relay of microbiota component-induced neuroinflammation in the dysregulation of the reward system following exposure to high-fat diet (HFD).</p><p><strong>Methods: </strong>Through a series of behavioural paradigms related to food-reward events and the use of pharmacological agents targeting the dopamine circuit, we investigated the mechanisms associated with the development of reward dysregulation during HFD-feeding in male mice. A Toll-like receptor 4 (TLR4) full knockout model and intraventricular lipopolysaccharide (LPS) diffusion at low doses, which mimics the obesity-associated neuroinflammatory phenotype, were used to investigate the causal roles of gut microbiota-derived components in neuroinflammation and reward dysregulation.</p><p><strong>Results: </strong>Our study revealed that short term exposure to HFD (24 h) tended to affect food-seeking behaviour, and this effect became significant after 1 week of HFD. Moreover, we found that deletion of TLR4 induced a partial protection against HFD-induced neuroinflammation and reward dysregulation. Finally, chronic brain diffusion of LPS recapitulated, at least in part, HFD-induced molecular and behavioural dysfunctions within the reward system.</p><p><strong>Conclusions: </strong>These findings highlight a link between the neuroinflammatory processes triggered by the gut microbiota components LPS and the dysregulation of the reward system during HFD-induced obesity through the TLR4 pathway, thus paving the way for future therapeutic approaches.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"21 1","pages":"305"},"PeriodicalIF":9.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sentinels of neuroinflammation: the crucial role of myeloid cells in the pathogenesis of gliomas and neurodegenerative diseases.","authors":"Blanca Cómitre-Mariano, Gabriel Vellila-Alonso, Berta Segura-Collar, Lucía Mondéjar-Ruescas, Juan M Sepulveda, Ricardo Gargini","doi":"10.1186/s12974-024-03298-y","DOIUrl":"10.1186/s12974-024-03298-y","url":null,"abstract":"<p><p>The inflammatory processes that drive pathologies of the central nervous system (CNS) are complex and involve significant contributions from the immune system, particularly myeloid cells. Understanding the shared and distinct pathways of myeloid cell regulation in different CNS diseases may offer critical insights into therapeutic development. This review aims to elucidate the mechanisms underlying myeloid cell dysfunction and neuroinflammation in two groups of neurological pathologies with significant social impact and a limited efficacy of their treatments: the most common primary brain tumors -gliomas-, and the most prevalent neurodegenerative disorders -Alzheimer's and Parkinson's disease. Despite their distinct clinical manifestations, these diseases share key pathological features, including chronic inflammation and immune dysregulation. The role of myeloid cells in neuroinflammation has garnered special interest in recent years in both groups, as evidenced by the growing focus on therapeutic research centred on myeloid cells. By examining the cellular and molecular dynamics that govern these conditions, we hope to identify common and unique therapeutic targets that can inform the development of more effective treatments. Recent advances in single-cell technologies have revolutionized our understanding of myeloid cell heterogeneity, revealing diverse phenotypes and molecular profiles across different disease stages and microenvironments. Here, we present a comprehensive analysis of myeloid cell involvement in gliomas, Alzheimer's and Parkinson's disease, with a focus on phenotypic acquisition, molecular alterations, and therapeutic strategies targeting myeloid cells. This integrated approach not only addresses the limitations of current treatments but also suggests new avenues for therapeutic intervention, aimed at modulating the immune landscape to improve patient outcomes.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"21 1","pages":"304"},"PeriodicalIF":9.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-37 suppresses CNS autoimmunity by increasing the frequency of Treg cells and reducing CD4 + T cell-derived IL-10 production.","authors":"Reza Yazdani, Hamed Naziri, Gholamreza Azizi, Bogoljub Ciric, Mozhde Askari, Amir Moghadam Ahmadi, Jaya Aseervatham, Guang-Xian Zhang, Abdolmohamad Rostami","doi":"10.1186/s12974-024-03295-1","DOIUrl":"10.1186/s12974-024-03295-1","url":null,"abstract":"<p><strong>Background: </strong>Interleukin-37 (IL-37) has anti-inflammatory properties in innate and adaptive immunity. Patients with multiple sclerosis (MS), an autoimmune inflammatory demyelinating disease of the central nervous system (CNS), have increased serum levels of IL-37. However, it is unknown whether IL-37 has an inhibitory effect on ongoing autoimmune neuroinflammation, thus offering a potential MS therapy.</p><p><strong>Aim: </strong>Here, we examined the effect of IL-37 in an experimental autoimmune encephalomyelitis (EAE) model after disease onset to determine if it was protective.</p><p><strong>Findings: </strong>IL-37-treated mice developed a less severe disease than control mice, with reduced demyelination as determined by increased expression of myelin basic protein. IL-37 suppressed inflammation by decreasing infiltration of CD4 + T cells into the CNS and increasing the frequency of regulatory T cells, while IL-10 expression by CD4 + T cells decreased over time in the CNS.</p><p><strong>Conclusion: </strong>Our findings confirm the immunomodulatory role of IL-37 in CNS inflammation during ongoing disease, thus indicating the potential of IL-37 as an inhibitory reagent for MS therapy.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"21 1","pages":"301"},"PeriodicalIF":9.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localization of brain neuronal IL-1R1 reveals specific neural circuitries responsive to immune signaling.","authors":"Daniel P Nemeth, Xiaoyu Liu, Marianne C Monet, Haichen Niu, Gabriella Maxey, Matt S Schrier, Maria I Smirnova, Samantha J McGovern, Anu Herd, Damon J DiSabato, Trey Floyd, Rohit R Atluri, Alex C Nusstein, Braedan Oliver, Kristina G Witcher, Joshua St Juste Ellis, Jasmine Yip, Andrew D Crider, Daniel B McKim, Paula A Gajewski-Kurdziel, Jonathan P Godbout, Qi Zhang, Randy D Blakely, John F Sheridan, Ning Quan","doi":"10.1186/s12974-024-03287-1","DOIUrl":"10.1186/s12974-024-03287-1","url":null,"abstract":"<p><p>Interleukin-1 (IL-1) is a pro-inflammatory cytokine that exerts a wide range of neurological and immunological effects throughout the central nervous system (CNS) and is associated with the etiology of affective and cognitive disorders. The cognate receptor for IL-1, Interleukin-1 Receptor Type 1 (IL-1R1), is primarily expressed on non-neuronal cells (e.g., endothelial cells, choroidal cells, ventricular ependymal cells, astrocytes, etc.) throughout the brain. However, the presence and distribution of neuronal IL-1R1 (nIL-1R1) has been controversial. Here, for the first time, a novel genetic mouse line that allows for the visualization of IL-1R1 mRNA and protein expression (Il1r1^GR/GR) was used to map all brain nuclei and determine the neurotransmitter systems which express nIL-1R1 in adult male mice. The direct responsiveness of nIL-1R1-expressing neurons to both inflammatory and physiological levels of IL-1β in vivo was tested. Neuronal IL-1R1 expression across the brain was found in discrete glutamatergic and serotonergic neuronal populations in the somatosensory cortex, piriform cortex, dentate gyrus, and dorsal raphe nucleus. Glutamatergic nIL-1R1 comprises most of the nIL-1R1 expression and, using Vglut2-Cre-Il1r1^r/r mice, which restrict IL-1R1 expression to only glutamatergic neurons, an atlas of glutamatergic nIL-1R1 expression across the brain was generated. Analysis of functional outputs of these nIL-1R1-expressing nuclei, in both Il1r1^GR/GR and Vglut2-Cre-Il1r1^r/r mice, reveals IL-1R1⁺ nuclei primarily relate to sensory detection, processing, and relay pathways, mood regulation, and spatial/cognitive processing centers. Intracerebroventricular (i.c.v.) injections of IL-1 (20 ng) induces NFκB signaling in IL-1R1⁺ non-neuronal cells but not in IL-1R1⁺ neurons, and in Vglut2-Cre-Il1r1^r/r mice IL-1 did not change gene expression in the dentate gyrus of the hippocampus (DG). GO pathway analysis of spatial RNA sequencing 1mo following restoration of nIL-1R1 in the DG neurons reveals IL-1R1 expression downregulates genes related to both synaptic function and mRNA binding while increasing select complement markers (C1ra, C1qb). Further, DG neurons exclusively express an alternatively spliced IL-1R Accessory protein isoform (IL-1RAcPb), a known synaptic adhesion molecule. Altogether, this study reveals a unique network of neurons that can respond directly to IL-1 via nIL-1R1 through non-autonomous transcriptional pathways; earmarking these circuits as potential neural substrates for immune signaling-triggered sensory, affective, and cognitive disorders.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"21 1","pages":"303"},"PeriodicalIF":9.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia-derived ADAM9 promote GHRH neurons pyroptosis by Mad2L2-JNK-caspase-1 pathway in subarachnoid hemorrhage.","authors":"Jian Mao, Yun Bao, Fan Liu, Qiyun Ye, Junxiang Peng, Jing Nie, Lijun Huang, Yonghong Liao, Yiheng Xing, Dongyang Wu, Ke Wang, Wenfeng Feng, Songtao Qi, Jun Pan, Binghui Qiu","doi":"10.1186/s12974-024-03299-x","DOIUrl":"10.1186/s12974-024-03299-x","url":null,"abstract":"<p><p>The incidence of growth hormone deficiency (GHD) after subarachnoid hemorrhage (SAH) is significantly higher than that of other neuroendocrine disorders, but the mechanism is still elusive. We used mass spectrometry to identify differentially expressed proteins in cerebrospinal fluid samples from a well-characterized cohort of patients. A total of 683 proteins were identified, including 39 upregulated proteins in the GHD group. ADAM9 was most highly associated with GHD. In vivo, ADAM9 colocalized with M1 microglia markers, GH and cognitive ability of mice decreased significantly, and microglia secreted ADAM9 significantly. ADAM9 regulates pyroptosis of GHRH neurons by the Mad2L2-JNK-caspase-1 pathway. Sorafenib inhibits ADAM9 secretion by microglia and improves GH levels and the cognitive ability of mice. This study found that the crosstalk between GHRH neurons and neuroglial cells in the hypothalamic arcuate nucleus, i.e., microglia, is an essential factor in the formation of GHD in SAH. We propose that neutralization of ADAM9 production by microglia might be a potential therapy for GHD after SAH.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"21 1","pages":"302"},"PeriodicalIF":9.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fueling neurodegeneration: metabolic insights into microglia functions.","authors":"Mohammadamin Sadeghdoust, Aysika Das, Deepak Kumar Kaushik","doi":"10.1186/s12974-024-03296-0","DOIUrl":"10.1186/s12974-024-03296-0","url":null,"abstract":"<p><p>Microglia, the resident immune cells of the central nervous system, emerge in the brain during early embryonic development and persist throughout life. They play essential roles in brain homeostasis, and their dysfunction contributes to neuroinflammation and the progression of neurodegenerative diseases. Recent studies have uncovered an intricate relationship between microglia functions and metabolic processes, offering fresh perspectives on disease mechanisms and possible treatments. Despite these advancements, there are still significant gaps in our understanding of how metabolic dysregulation affects microglial phenotypes in these disorders. This review aims to address these gaps, laying the groundwork for future research on the topic. We specifically examine how metabolic shifts in microglia, such as the transition from oxidative phosphorylation and mitochondrial metabolism to heightened glycolysis during proinflammatory states, impact the disease progression in Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Additionally, we explore the role of iron, fatty and amino acid metabolism in microglial homeostasis and repair. Identifying both distinct and shared metabolic adaptations in microglia across neurodegenerative diseases could reveal common therapeutic targets and provide a deeper understanding of disease-specific mechanisms underlying multiple CNS disorders.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"21 1","pages":"300"},"PeriodicalIF":9.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}