Journal of Neurochemistry最新文献

{"title":"Tubulin-Binding Region Modulates Cholesterol-Triggered Aggregation of Tau Proteins","authors":"Abid Ali,&nbsp;Mikhail Matveyenka,&nbsp;Davis N. Pickett,&nbsp;Axell Rodriguez,&nbsp;Dmitry Kurouski","doi":"10.1111/jnc.16294","DOIUrl":"10.1111/jnc.16294","url":null,"abstract":"<div>\u0000 \u0000 <p>A hallmark of Alzheimer disease (AD) and tauopathies, severe neurodegenerative diseases, is the progressive aggregation of Tau, also known as microtubule-associated Tau protein. Full-length Tau_1-441, also known as 2N4R, contains two N-terminal inserts that bind to tubulin. This facilitates the self-assembly of tubulin simultaneously enhancing stability of cell microtubules. Other Tau isoforms have one (1N4R) or zero (0N4R) N-terminal inserts, which makes 2N4R Tau more and 0N4R less effective in promoting microtubule self-assembly. A growing body of evidence indicates that lipids can alter the aggregation rate of Tau isoforms. However, the role of N-terminal inserts in Tau-lipid interactions remains unclear. In this study, we utilized a set of biophysical methods to determine the extent to which N-terminal inserts alter interactions of Tau isoforms with cholesterol, one of the most important lipids in plasma membranes. Our results showed that 2 N insert prevents amyloid-driven aggregation of Tau at the physiological concentration of cholesterol, while the absence of this N-terminal repeat (1N4R and 0N4R Tau) resulted in the self-assembly of Tau into toxic amyloid fibrils. We also found that the presence of cholesterol in the lipid bilayers caused a significant increase in the cytotoxicity of 1N4R and 0N4R Tau to neurons. This effect was not observed for 2N4R Tau fibrils formed in the presence of lipid membranes with low, physiological, and elevated concentrations of cholesterol. Using molecular assays, we found that Tau aggregates primarily exert cytotoxicity by damaging cell endosomes, endoplasmic reticulum, and mitochondria.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indole and Coumarin Derivatives Targeting EEF2K in Aβ Folding Reporter Cells","authors":"Shun-Tzu Chi,&nbsp;Pei-Cih Wei,&nbsp;Ya-Jen Chiu,&nbsp;Te-Hsien Lin,&nbsp;Chih-Hsin Lin,&nbsp;Chiung-Mei Chen,&nbsp;Ching-Fa Yao,&nbsp;Wenwei Lin,&nbsp;Guey-Jen Lee-Chen,&nbsp;Kuo-Hsuan Chang","doi":"10.1111/jnc.16300","DOIUrl":"10.1111/jnc.16300","url":null,"abstract":"<div>\u0000 \u0000 <p>Misfolding and accumulation of amyloid-β (Aβ) in the brains of patients with Alzheimer's disease (AD) lead to neuronal loss through various mechanisms, including the downregulation of eukaryotic elongation factor 2 (EEF2) protein synthesis signaling. This study investigated the neuroprotective effects of indole and coumarin derivatives on Aβ folding and EEF2 signaling using SH-SY5Y cells expressing Aβ-green fluorescent protein (GFP) folding reporter. Among the tested compounds, two indole (NC009-1, -6) and two coumarin (LM-021, -036) derivatives effectively reduced Aβ misfolding and associated reactive oxygen species (ROS) production. Additionally, these compounds decreased acetylcholinesterase and caspase-3/-6 activities while promoting neurite outgrowth. NC009-1 increased active phosphorylation of extracellular-signal regulated kinase (ERK) (T202/Y204), leading to an increase in inactive eukaryotic elongation factor 2 kinase (EEF2K) phosphorylation (S366). LM-021 decreased the active phosphorylation of AMP-activated protein kinase (AMPK) (T172) and EEF2K (S398), while LM-036 exhibited dual effects, increasing inactive phosphorylation and decreasing active phosphorylation of EEF2K. These changes in EEF2K phosphorylation led to decreased EEF2K activity and a subsequent reduction in inactive phosphorylation of EEF2 (T56). This cascade further promoted the phosphorylation of transcription factor cAMP-response-element binding protein (CREB) (S133) and the expression of brain-derived neurotrophic factor (BDNF), and reduced BCL-2 associated X-protein (BAX)/B-cell lymphoma 2 (BCL2) ratio. Knockdown of EEF2 abolished the effects of NC009-1, LM-021, and LM-036 on CREB phosphorylation, BDNF expression, caspase-3 activity, and neurite outgrowth. These findings demonstrate that NC009-1, LM-021, and LM-036 exert their neuroprotective effects through modulation of EEF2K signaling, highlighting their potentials as therapeutic candidates for AD.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Glucocorticoid-Associated Stress-Like Conditions on Aquaporin-4 in Cultured Astrocytes and Its Modulation by Adenosine A2A Receptors","authors":"Liliana Dias,&nbsp;Ana Margarida Nabais,&nbsp;Vladimir P. P. Borges-Martins,&nbsp;Paula M. Canas,&nbsp;Rodrigo A. Cunha,&nbsp;Paula Agostinho","doi":"10.1111/jnc.16299","DOIUrl":"10.1111/jnc.16299","url":null,"abstract":"<div>\u0000 \u0000 <p>Astrocytes participate in brain clearance of extracellular proteins and metabolites, through the activity of the water channel aquaporin-4 (AQP4), which can be deregulated in stress-related disorders, impairing brain waste clearance. The present study investigates the impact of dexamethasone (Dexa), a synthetic glucocorticoid used as a simplified in vitro stress model, on astrocytic AQP4 and its modulation by adenosine A_2A receptors (A_2AR), which blockade reverses conditions related with maladaptive stress, such as anxiety and depression. The clearance of proteins in primary astrocytic cultures, assessed using 5 kDa FITC-dextran and 45 kDa TRITC-dextran uptake, was decreased by a 24 h exposure to 100 nM Dexa. The Dexa exposure decreased α-syntrophin density, a protein-targeting AQP4 to astrocytic processes, potentially affecting AQP4 location and, consequently, its activity. Accordingly, Dexa exposure decreased astrocytic water influx (assessed with calcein fluorescence), which paralleled the impairment of dextran clearance. The Dexa-induced decrease in extracellular protein uptake was prevented by the AQP4 activator TGN-073 and A_2AR antagonism with SCH58261, showing that the impairment of AQP4-mediated protein clearance was controlled by A_2AR in this Dexa-simplified <i>in vitro</i> stress model. Additionally, the effects of Dexa in AQP4 location and activity were prevented by SCH58261, confirming that A_2AR modulate AQP4 function. This conclusion was reinforced by the observed AQP4/A_2AR physical interaction in astrocytes. Overall, the data indicate that <i>in vitro</i> conditions related to stress affect the localisation of astrocytic AQP4 and its role in extracellular protein uptake, which was modulated by A_2AR. These findings unveil a novel therapeutic mechanism to prevent brain extracellular protein accumulation and associated neurological disorders by tinkering with AQP4 and A_2AR.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher CSF sTREM2 attenuates APOE ε4-related risk for amyloid pathology in cognitively intact adults: The CABLE study","authors":"Yong-Chang Wang,&nbsp;Liang-Yu Huang,&nbsp;Hai-Hua Guo,&nbsp;Min Liu,&nbsp;Yu-Ying Zhang,&nbsp;Zi-Qi Zhang,&nbsp;Quan Hao,&nbsp;Chen-Chen Tan,&nbsp;Lan Tan","doi":"10.1111/jnc.16273","DOIUrl":"10.1111/jnc.16273","url":null,"abstract":"<p>The triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein found in microglia within the brain, and its soluble form (sTREM2) has been shown to reduce amyloid deposition. Whether elevated TREM2-mediated microglial activity decreases the risk of Alzheimer's disease (AD) is unclear. The aim of this study was to assess whether high cerebrospinal fluid (CSF) levels of sTREM2 attenuate the risk of <i>APOE ε4</i>-associated amyloid pathology. We included 877 cognitively intact subjects from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, including <i>APOE ε4</i> carriers (<i>n</i> = 136) and non-carriers (<i>n</i> = 741). The linear regression was used to examine the interaction effect between CSF sTREM2 levels and APOE ε4 status on CSF Aβ42 levels. Additionally, subgroup analyses stratified by sex and age were conducted. Our main finding was that higher concentrations of CSF sTREM2 attenuated the effect of <i>APOE ε4</i> carriage (i.e., the sTREM2 × <i>APOE ε4</i> interaction) on amyloid deposition (<i>β</i> = −2.701e-05, <i>p</i> = 0.023). Subgroup analyses showed that the effect of interaction was still significant only in male (<i>p</i> = 0.041) and mid-life (<i>p</i> = 0.013) subgroups. Our study suggested that in cognitively intact individuals, changes in sTREM2 levels are associated with biomarkers of AD, and higher concentrations of CSF sTREM2 attenuated the risk of <i>APOE ε4</i>-related amyloid pathology. The identified role of the sTREM2 × <i>APOE ε4</i> interaction in amyloid pathology offers new insights into potential strategies for AD prevention in <i>APOE ε4</i> carriers.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasticity of Mouse Dorsal Root Ganglion Neurons by Innate Immune Activation Is Influenced by Electrophysiological Activity","authors":"Timothy N. Friedman,&nbsp;Shawn M. Lamothe,&nbsp;Aislinn D. Maguire,&nbsp;Thomas Hammond,&nbsp;Gustavo Tenorio,&nbsp;Brett J. Hilton,&nbsp;Jason R. Plemel,&nbsp;Harley T. Kurata,&nbsp;Bradley J. Kerr","doi":"10.1111/jnc.16292","DOIUrl":"10.1111/jnc.16292","url":null,"abstract":"<p>The complex relationship between inflammation, its effects on neuronal excitability and the ensuing plasticity of dorsal root ganglion (DRG) sensory neurons remains to be fully explored. In this study, we have employed a system of experiments assessing the impact of inflammatory conditioned media derived from activated immune cells on the excitability and activity of DRG neurons and how this relates to subsequent growth responses of these cells. We show here that an early phase of increased neuronal activity in response to inflammatory conditioned media is critical for the engagement of plastic processes and that neuronal excitability profiles are linked through time to the structural phenotype of individual neurons. Pharmacological blockade of neuronal activity was able to abolish the growth-promoting effects of inflammatory media. Our results suggest that targeting the activity of DRG neurons may provide a novel therapeutic avenue to manipulate their growth status and potential for plasticity in response to inflammation. Importantly, the same pharmacological blockade in vivo abolished pain responses in a mouse model of multiple sclerosis. While further studies are needed to fully elucidate the underlying mechanisms of the relationship between neural activity and growth status, a more complete understanding of this relationship may ultimately lead to the development of new treatments for neuropathic pain in disorders associated with heightened immune responses such as rheumatoid arthritis and multiple sclerosis.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Role of Ccn3 in Type III Cell of Mice Taste Buds","authors":"Kuanyu Wang,&nbsp;Yoshihiro Mitoh,&nbsp;Kengo Horie,&nbsp;Ryusuke Yoshida","doi":"10.1111/jnc.16291","DOIUrl":"10.1111/jnc.16291","url":null,"abstract":"<p>Different taste cells express unique cell-type markers, enabling researchers to distinguish them and study their functional differentiation. Using single-cell RNA-Seq of taste cells in mouse fungiform papillae, we found that Cellular Communication Network Factor 3 (<i>Ccn3</i>) was highly expressed in Type III taste cells but not in Type II taste cells. <i>Ccn3</i> is a protein-coding gene involved in various biological processes, such as cell proliferation, angiogenesis, tumorigenesis, and wound healing. Therefore, in this study, we aimed to explore the expression and function of <i>Ccn3</i> in mouse taste bud cells. Using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry (IHC), we confirmed that <i>Ccn3</i> was predominantly expressed in Type III taste cells. Through IHC, quantitative real-time RT-PCR, gustatory nerve recordings, and short-term lick tests, we observed that <i>Ccn3</i> knockout (<i>Ccn3</i>-KO) mice did not exhibit any significant differences in the expression of taste cell markers and taste responses compared to wild-type controls. To explore the function of <i>Ccn3</i> in taste cells, bioinformatics analyses were conducted and predicted possible roles of <i>Ccn3</i> in tissue regeneration, perception of pain, protein secretion, and immune response. Among them, an immune function is the most plausible based on our experimental results. In summary, our study indicates that although <i>Ccn3</i> is strongly expressed in Type III taste cells, its knockout did not influence the basic taste response, but bioinformatics provided valuable insights into the possible role of <i>Ccn3</i> in taste buds and shed light on future research directions.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding stress-induced transmission of peripherally derived factors into the brain and responses in non-neuronal cells","authors":"Mikiko Kudo,&nbsp;Shota Yamamoto,&nbsp;Shin-ichiro Hiraga,&nbsp;Takahiro Masuda","doi":"10.1111/jnc.16262","DOIUrl":"10.1111/jnc.16262","url":null,"abstract":"<p>Stress is a significant cause of mental disorders, for which effective treatments remain limited due to an insufficient understanding of its pathogenic mechanisms. Recent research has increasingly focused on non-neuronal cells to elucidate the molecular mechanisms underlying psychopathology. In this review, we summarize the current knowledge on how non-neuronal cells in the central nervous system, including microglia, astrocytes, and oligodendrocytes, respond to peripherally derived stress-related factors and how these responses contribute to the development of mental disorders. A more comprehensive understanding of stress-induced alterations, with careful consideration of the type and timing of stress exposure, will provide fundamental insights into the pathogenesis of diverse stress-related mental disorders.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.16262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative single-cell RNA-seq and ATAC-seq analysis of the evolutionary trajectory features of adipose-derived stem cells induced into astrocytes","authors":"Qingxi Long,&nbsp;Yi Yuan,&nbsp;Ya Ou,&nbsp;Wen Li,&nbsp;Qi Yan,&nbsp;Pingshu Zhang,&nbsp;Xiaodong Yuan","doi":"10.1111/jnc.16269","DOIUrl":"https://doi.org/10.1111/jnc.16269","url":null,"abstract":"<p>This study employs single-cell RNA sequencing (scRNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing technologies (scATAC-seq) to perform joint sequencing on cells at various time points during the induction of adipose-derived stem cells (ADSCs) into astrocytes. We applied bioinformatics approaches to investigate the differentiation trajectories of ADSCs during their induced differentiation into astrocytes. Pseudotemporal analysis was used to infer differentiation trajectories. Additionally, we assessed chromatin accessibility patterns during the differentiation process. Key transcription factors driving the differentiation of ADSCs into astrocytes were identified using motif and footprint methods. Our analysis revealed significant shifts in gene expression during the induction process, with astrocyte-related genes upregulated and stem cell-related genes downregulated. ADSCs first differentiated into neural stem cell-like cells with high plasticity, which further matured into astrocytes via two distinct pathways. Marked changes in chromatin accessibility were observed during ADSC-induced differentiation, affecting transcription regulation and cell function. Transcription factors analysis identified NFIA/B/C/X and CEBPA/B/D as key regulators in ADSCs differentiation into astrocytes. We observed a correlation between chromatin accessibility and gene expression, with ADSCs exhibiting broad chromatin accessibility prior to lineage commitment, where chromatin opening precedes transcription initiation. In summary, we found that ADSCs first enter a neural stem cell-like state before differentiating into astrocytes. ADSCs also display extensive chromatin accessibility prior to astrocyte differentiation, although transcription has not yet been initiated. These findings offer a theoretical framework for understanding the molecular mechanisms underlying this process.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered metabolic function induced by Aβ-oligomers and PSEN1 mutations in iPSC-derived astrocytes","authors":"Richard J. Elsworthy,&nbsp;Mattea J. Finelli,&nbsp;Sarah Aqattan,&nbsp;Connor Dunleavy,&nbsp;Marianne King,&nbsp;Adele Ludlam,&nbsp;Marta A. Tarczyluk,&nbsp;Sophie L. Allen,&nbsp;Sophie Prosser,&nbsp;Rui Chen,&nbsp;Sandra Martinez Jarquin,&nbsp;Dong H. Kim,&nbsp;James Brown,&nbsp;H. R. Parri,&nbsp;Sarah Aldred,&nbsp;Eric J. Hill","doi":"10.1111/jnc.16267","DOIUrl":"10.1111/jnc.16267","url":null,"abstract":"<p>Altered energy metabolism in Alzheimer's disease (AD) is a major pathological hallmark implicated in the early stages of the disease process. Astrocytes play a central role in brain homeostasis and are implicated in multiple neurodegenerative diseases. Although numerous studies have investigated global changes in brain metabolism, redox status, gene expression and epigenetic markers in AD, the intricate interplay between different metabolic processes, particularly in astrocytes, remains poorly understood. Numerous studies have implicated amyloid-β and the amyloid-β precursor in the development and progression of AD. To determine the effects of amyloid-β peptides or the impact of amyloid-β precursor protein processing on astrocyte metabolism, we differentiated astrocytes from induced pluripotent stem cells derived from people with early onset familial AD and controls. This study demonstrates that familial AD-derived astrocytes exhibit significantly more changes in their metabolism including glucose uptake, glutamate uptake and lactate release, with increases in oxidative and glycolytic metabolism compared to acute amyloid-β exposure. In addition to changes in major metabolic pathways including glutamate, purine and arginine metabolism and the citric acid cycle, we demonstrate evidence of gliosis in familial AD astrocytes highlighting a potential pathological hallmark. This suggests that chronic alterations in metabolism may occur very early in the disease process and present significant risk factors for disease progression for patients with early onset AD. These findings may also reveal important drivers of disease in late onset dementia and highlights key targets for potential diagnostic features and therapeutic agents in the future.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.16267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fundamental Neurochemistry Review: Lipids across microglial states","authors":"Marianela E. Traetta,&nbsp;Haley A. Vecchiarelli,&nbsp;Marie-Ève Tremblay","doi":"10.1111/jnc.16259","DOIUrl":"10.1111/jnc.16259","url":null,"abstract":"<p>The capacity of immune cells to alter their function based on their metabolism is the basis of the emerging field of immunometabolism. Microglia are the resident innate immune cells of the central nervous system, and it is a current focus of the field to investigate how alterations in their metabolism impact these cells. Microglia have the ability to utilize lipids, such as fatty acids, as energy sources, but also alterations in lipids can impact microglial form and function. Recent studies highlighting different microglial states and transcriptional signatures have highlighted modifications in lipid processing as defining these states. This review highlights these recent studies and uses these altered pathways to discuss the current understanding of lipid biology in microglia. The studies highlighted here review how lipids may alter microglial phagocytic functioning or alter their pro- and anti-inflammatory balance. These studies provide a foundation by which lipid supplementation or diet alterations could influence microglial states and function. Furthermore, targets modulating microglial lipid metabolism may provide new treatment avenues.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.16259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}