Neurochemistry international最新文献

{"title":"The role of mitochondrial remodeling in neurodegenerative diseases","authors":"Duanqin Guan ,&nbsp;Congmin Liang ,&nbsp;Dongyan Zheng ,&nbsp;Shizhen Liu ,&nbsp;Jiankun Luo ,&nbsp;Ziwei Cai ,&nbsp;He Zhang ,&nbsp;Jialong Chen","doi":"10.1016/j.neuint.2024.105927","DOIUrl":"10.1016/j.neuint.2024.105927","url":null,"abstract":"<div><div>Neurodegenerative diseases are a group of diseases that pose a serious threat to human health, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS). In recent years, it has been found that mitochondrial remodeling plays an important role in the onset and progression of neurodegenerative diseases. Mitochondrial remodeling refers to the dynamic regulatory process of mitochondrial morphology, number and function, which can affect neuronal cell function and survival by regulating mechanisms such as mitochondrial fusion, division, clearance and biosynthesis. Mitochondrial dysfunction is an important intrinsic cause of the pathogenesis of neurodegenerative diseases. Mitochondrial remodeling abnormalities are involved in energy metabolism in neurodegenerative diseases. Pathological changes in mitochondrial function and morphology, as well as interactions with other organelles, can affect the energy metabolism of dopaminergic neurons and participate in the development of neurodegenerative diseases. Since the number of patients with PD and AD has been increasing year by year in recent years, it is extremely important to take effective interventions to significantly reduce the number of morbidities and to improve people's quality of life. More and more researchers have suggested that mitochondrial remodeling and related dynamics may positively affect neurodegenerative diseases in terms of neuronal and self-adaptation to the surrounding environment. Mitochondrial remodeling mainly involves its own fission and fusion, energy metabolism, changes in channels, mitophagy, and interactions with other cellular organelles. This review will provide a systematic summary of the role of mitochondrial remodeling in neurodegenerative diseases, with the aim of providing new ideas and strategies for further research on the treatment of neurodegenerative diseases.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105927"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969080","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":"Inhibition of Kv1.1 channels ameliorates Cu(II)-induced microglial activation and cognitive impairment in mice","authors":"Wenwen Ni ,&nbsp;Jiani Ding ,&nbsp;Ping Gong ,&nbsp;Xiaofang Tan,&nbsp;Juan Li","doi":"10.1016/j.neuint.2025.105936","DOIUrl":"10.1016/j.neuint.2025.105936","url":null,"abstract":"<div><div>Microglia-mediated neuroinflammation plays a critical role in neuronal damage in neurodegenerative disorders such as Alzheimer's disease. Evidence shows that voltage-gated potassium (Kv) channels regulate microglial activation. We previously reported that copper dyshomeostasis causes neuronal injury via activating microglia. This study was designed to explore the role of Kv1.1 channels in copper-evoked microglial neuroinflammation. BV-2 microglial cells were treated with Cu(II). DiBAC4(3) was used to measure membrane potential. Microglial activation and neuronal loss were detected by enzyme-linked immunosorbent assay, Western blotting, and immunostaining. Learning and memory function was assessed with Morris water maze task. Cu(II) caused a hyperpolarized membrane potential in microglial cells, an effect abolished by functional Kv1.1 blockade. Blockade of Kv1.1 and knock-down of Kv1.1 with small interfering RNA repressed Cu(II)-induced microglial production of pro-inflammatory mediators. Also, Kv1.1 inhibition attenuated activation of PI3K/Akt-ERK1/2 signaling pathway and production of mitochondrial reactive oxidative species as well as nuclear factor-κB activation in Cu(II)-stimulated microglia. Moreover, the Cu(II)-caused, microglia-mediated neurotoxicity (indicated by reduced neuronal survival and increased dendritic loss) was attenuated by Kv1.1 knock-down. In an <em>in vivo</em> mouse model, hippocampal injection of Cu(II) caused elevated Kv1.1 mRNA (but not other Kv1 channels) expression and enhanced microglial Kv1.1 immunoreactivity in the hippocampus. Furthermore, blockade of Kv1.1 attenuated Cu(II)-induced microglial activation and neuronal dendritic loss in the hippocampus and learning and memory dysfunction. These findings suggest that inhibition of Kv1.1 ameliorates Cu(II)-induced microglial activation and cognitive impairment. Thus, it might represent a potential molecular target for anti-inflammatory therapy of neurodegenerative disorders.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105936"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997944","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":"HIF-1α downregulates the APP protein after oxygen and glucose deprivation in the APPswe/PSEN1 mouse model of Alzheimer's disease","authors":"Mario Villa-González ,&nbsp;Marta García-Juan ,&nbsp;Lara Ordóñez-Gutiérrez ,&nbsp;María José Pérez-Álvarez ,&nbsp;Francisco Wandosell Jurado","doi":"10.1016/j.neuint.2024.105923","DOIUrl":"10.1016/j.neuint.2024.105923","url":null,"abstract":"<div><div>The mTORC1 and AMPK signalling pathways are considered key nodes regulating anabolism and catabolism, and they are altered in certain processes of neurodegeneration such as hypoxia associated with ischemic stroke or Alzheimer's disease. The lack of oxygen and/or glucose (oxygen and glucose deprivation-OGD) may affect the equilibrium of the mTORC1/AMPK pathways, perhaps aggravating neurodegeneration. The alteration of these pathways mediated by OGD may be reflected in other alterations, such as the activation of autophagy that could in turn modify the secretion/accumulation of amyloid-β, one of the two histopathological markers of Alzheimer's disease. Accordingly, we set out to analyze whether OGD enhances autophagy and its implication in neuronal amyloidosis. The data obtained reveal that OGD significantly dampens not only neuronal amyloid-β production but also, the total APP protein levels, without affecting BACE-1 levels. We show that this mechanism is independent of cellular proteolysis (autophagy or proteasome) and that it can be partially recovered by inhibiting HIF-1α activity.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105923"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132626","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":"Ferritinophagy promotes microglia ferroptosis to aggravate neuroinflammation induced by cerebral ischemia-reperfusion injury via activation of the cGAS-STING signaling pathway","authors":"Haijing Sui ,&nbsp;Zhenyu Sun ,&nbsp;Chang Liu ,&nbsp;Hongjie Xi","doi":"10.1016/j.neuint.2024.105920","DOIUrl":"10.1016/j.neuint.2024.105920","url":null,"abstract":"<div><div>Cerebral ischemia-reperfusion injury (CIRI) is a common and serious complication of reperfusion therapy in patients with ischemic stroke (IS). The regulation of microglia-mediated neuroinflammation to control CIRI has garnered considerable attention. The balance of iron metabolism is key to maintaining the physiological functions of microglia. Nuclear Receptor Coactivator 4 (NCOA4)-mediated ferritinophagy, an important pathway in regulating iron metabolism, is a promising intervention target. However, studies on the impacts of ferritinophagy on microglia-mediated neuroinflammation are lacking. This study aimed to identify potential treatments for CIRI-induced neuroinflammation by focusing on ferritinophagy and the specific mechanisms whereby iron metabolism regulates microglia-mediated neuroinflammation. CIRI induced the activation of ferritinophagy in microglia, characterized by the upregulation of NCOA4, downregulation of Ferritin Heavy Chain 1 (FTH1), and increased intracellular iron levels. This activation contributes to increased ferroptosis, oxidative stress, and the release of inflammatory factors. Silencing NCOA4 or application of the ferroptosis-specific inhibitor Ferrostatin-1 (Fer-1) effectively suppressed the CIRI-induced damage <em>in vivo</em> and <em>in vitro</em>. While Fer-1 addition did not inhibit the CIRI-activated ferritinophagy, it did partially reverse the alleviation of NCOA4 depletion-induced neuroinflammation, suggesting that ferroptosis is an essential intermediate step in ferritinophagy-induced neuroinflammatory damage. Furthermore, using IS-related transcriptomic data, the cGAS-STING pathway was identified as a crucial mechanism connecting ferritinophagy and ferroptosis. Specific inhibition of the cGAS-STING pathway reduced ferritinophagy-induced ferroptosis and neuroinflammation. In summary, our results indicated that ferritinophagy activates the cGAS-STING signaling pathway, which promotes the inflammatory response and oxidative stress in microglia in a ferroptosis-dependent manner, thereby exacerbating CIRI-induced neuroinflammation. These findings provide theoretical support for the clinical treatment of CIRI.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105920"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891172","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":"Brain endocannabinoid control of metabolic and non-metabolic feeding behaviors","authors":"Maoxing Zhang ,&nbsp;Qingyu Wang ,&nbsp;Ying Wang","doi":"10.1016/j.neuint.2024.105921","DOIUrl":"10.1016/j.neuint.2024.105921","url":null,"abstract":"<div><div>The central endocannabinoid (eCB) system in brain shows a crucial role in the regulation of feeding behaviors, influencing both metabolic and non-metabolic mechanisms of appetite control, which has been paid much attention. Although there are already many review articles discussing eCB modulation of feeding behaviors, our paper attempts to summarize the recent advancements through synapses, circuits, and network in brain. Our focus is on the dual role of eCB signalling in regulating metabolic energy balance and hedonic reward-related feeding. In the context of metabolic regulation of feeding behaviors, eCBs affect the hypothalamic circuits that balance hunger and satiety through signal integration related to energy status and nutrient availability. Dysregulation of this system can contribute to metabolic disorders such as obesity and anorexia. In non-metabolic feeding, the eCB system influences the hedonic aspects of eating by modulating reward pathways, including the mesolimbic system and the olfactory bulb, critical for motivating food intake and processing sensory cues. This review also explores therapeutic strategies targeting the eCB system, including cannabinoid receptor antagonists and eCB hydrolase enzyme inhibitors, which hold promise for treating conditions associated with appetite dysregulation and eating disorders. By synthesizing recent findings, we aim to highlight the intricate mechanisms through which the eCB system affects feeding behavior and to propose future directions for research and therapeutic intervention in the realm of appetite control and eating disorders.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105921"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870921","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":"Anatomizing causal relationships between gut microbiota, plasma metabolites, and epilepsy: A mendelian randomization study","authors":"Xi Wang ,&nbsp;Haowen Duan ,&nbsp;Fengfei Lu ,&nbsp;Xinyue Yu,&nbsp;Minghan Xie,&nbsp;Peiyi Chen,&nbsp;Junjie Zou,&nbsp;Lijie Gao,&nbsp;Yingqian Cai,&nbsp;Rongqing Chen,&nbsp;Yanwu Guo","doi":"10.1016/j.neuint.2024.105924","DOIUrl":"10.1016/j.neuint.2024.105924","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy causes a heavy disease burden, and the gut microbiota (GM) influences the progression of epilepsy, while plasma metabolites directly or indirectly associated with GM may play a mediating role. However, the causal relationships between epilepsy, GM, and potential metabolite mediators are lack of investigation.</div></div><div><h3>Methods</h3><div>Mendelian randomization (MR) analysis was applied to estimate the effects of GM and plasma metabolites on epilepsy. Genetic instruments were obtained from large-scale genome-wide meta-analysis of GM (n = 5959), plasma metabolites (n = 136,016), and epilepsy (Cases/controls = 12891/312803) of European ancestry. Epilepsy phenotypes included all epilepsy, generalized epilepsy and focal epilepsy from the Finn Gen R10 database. And two-step MR (TSMR) to discover the potential mediating metabolites.</div></div><div><h3>Results</h3><div>In total, we found 19 gut microbial taxa to be causally associated with the risk of epilepsy, among which <em>Omnitrophota</em> phylum had the strongest association (OR, 2.3; <em>P</em> = 0.009) with promoting effect. We also identified 21 plasma metabolites associated with epilepsy, the strongest ones of which are eastotal fatty acids (OR, 1.12; <em>P</em> = 0.001) that exhibited a facilitating effect. We observed indirect effects of free cholesterol to total lipids ratio in large LDL in associations between <em>Fournierella massiliensis</em> species and epilepsy, with a mediated proportion of −3.64% (95%CI, -7.22%∼-0.06%; <em>P</em> = 0.046).</div></div><div><h3>Conclusion</h3><div>This study supports a causal link between <em>Fournierella massiliensis</em> species, free cholesterol to total lipids ratio in large LDL and epilepsy, as well as a mediating effect of free cholesterol to total lipids ratio in large LDL in epilepsy.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105924"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913477","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":"Discovery of the therapeutic potential of naltriben against glutamate-induced neurotoxicity","authors":"Hyomin Ahn ,&nbsp;Hyomin Lee ,&nbsp;Wonseok Choi ,&nbsp;Hyebin Lee ,&nbsp;Kang-Gon Lee ,&nbsp;Inchan Youn ,&nbsp;Wooyoung Hur ,&nbsp;Sungmin Han ,&nbsp;Chiman Song","doi":"10.1016/j.neuint.2025.105928","DOIUrl":"10.1016/j.neuint.2025.105928","url":null,"abstract":"<div><div>Glutamate-induced neuronal death is associated with neurodegeneration including cerebral ischemia. Several μ-opioid receptor antagonists exhibit a neuroprotective activity and have been considered as a potential therapeutic option for neurodegenerative disorders. For the first time, our current study unveiled the neuroprotective activity of selective δ-opioid receptor antagonists. A potent, selective δ-opioid receptor antagonist naltriben, also known as a potent TRPM7 agonist, displayed the prominent protective effect against glutamate-induced toxicity through opioid receptor-independent, TRPM7-independent mechanisms in HT22 cells. Naltriben activated Nrf2 pathway, and alleviated glutamate-induced Ca²⁺ influx, ROS production, and apoptosis. Moreover, intraperitoneal administration of naltriben at 20 mg/kg greatly reduced the infarct volume in the subcortical photothrombotic ischemia mouse model <em>in vivo</em>. The neuroprotective activity of naltriben was enhanced by a longer pretreatment, indicating that like Nrf2 activators, naltriben also requires the cellular priming for its full protective effects. Together, these results suggested naltriben as a potential therapeutic agent in conditions related with glutamate-induced neurotoxicity.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105928"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930418","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":"Sigma-1 receptor activation produces faster antidepressant-like effect through enhancement of hippocampal neuroplasticity: Focus on sigma-1-5-HT1A heteroreceptor complex","authors":"Peng Ren ,&nbsp;Jing-Ya Wang ,&nbsp;Meng-Jie Xu ,&nbsp;Hong-Lei Chen ,&nbsp;Jing-Yao Duan ,&nbsp;Yun-Feng Li","doi":"10.1016/j.neuint.2025.105937","DOIUrl":"10.1016/j.neuint.2025.105937","url":null,"abstract":"<div><div>The sigma-1 receptor (S1R) has garnered significant attention as a potential target for rapid-onset antidepressant-like effects, particularly owing to its ability to swiftly stimulate serotonergic neurons in the dorsal raphe nucleus (DRN). However, the precise mechanisms underlying its regulatory effects remain unclear. Therefore, this study aims to examine the interaction between SA-4503 (a selective S1R agonist) and 8-OH-DPAT (a serotonin1A (5-HT1A) receptor agonist) in mice with depressive-like behavior induced by chronic restraint stress (CRS). Preliminary studies were conducted to explore the potential mechanisms underlying the accelerated antidepressant-like effects resulting from the combined activation of S1R and 5-HT1A receptors. The results showed that the coadministration of SA4503 (1.0 mg/kg, orally) and 8-OH-DPAT (0.3 mg/kg, i. g.) produced antidepressant-like effects. However, the doses of 8-OH-DPAT used in this study did not exhibit intrinsic antidepressant-like activity in this model. Moreover, using an <em>in-situ</em> proximity ligation assay provided the first evidence of S1R-5-HT1A heteroreceptor complexes in the midbrain DRN and dentate gyrus (DG) of the forebrain in mice. The formation of these heterocomplexes was influenced by pharmacological agents and was closely associated with depressive-like behavior development in mice. Mechanistic analysis revealed that the combined activation of S1R and 5-HT1A receptors synergistically enhanced neurogenesis and plasticity in the dorsal DG region of the hippocampus in mice subjected to CRS. These findings significantly advance our understanding of S1R-mediated neuroplasticity, suggesting potential therapeutic strategies for developing rapid-acting antidepressants.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"184 ","pages":"Article 105937"},"PeriodicalIF":4.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063048","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":"TDP-43 transports ferritin heavy chain mRNA to regulate oxidative stress in neuronal axons","authors":"Jyunki Jinno ,&nbsp;Rehab F. Abdelhamid ,&nbsp;Junko Morita ,&nbsp;Ryoko Saga ,&nbsp;Yusuke Yamasaki ,&nbsp;Atsushi Kadowaki ,&nbsp;Kotaro Ogawa ,&nbsp;Yasuyoshi Kimura ,&nbsp;Kensuke Ikenaka ,&nbsp;Goichi Beck ,&nbsp;Kousuke Baba ,&nbsp;Yoshitaka Nagai ,&nbsp;Emiko Kasahara ,&nbsp;Atsuo Sekiyama ,&nbsp;Tasuku Hirayama ,&nbsp;Isao Hozumi ,&nbsp;Tatsuya Hasegawa ,&nbsp;Toshiyuki Araki ,&nbsp;Hideki Mochizuki ,&nbsp;Seiichi Nagano","doi":"10.1016/j.neuint.2025.105934","DOIUrl":"10.1016/j.neuint.2025.105934","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis (ALS) is characterized by the mislocalization and abnormal deposition of TAR DNA-binding protein 43 (TDP-43). This protein plays important roles in RNA metabolism and transport in motor neurons and glial cells. In addition, abnormal iron accumulation and oxidative stress are observed in the brain and spinal cord of patients with ALS exhibiting TDP-43 pathology and in animal models of ALS. We have previously demonstrated that TDP-43 downregulation significantly affects the expression of ferritin heavy chain (<em>Fth1</em>) mRNA in the axonal regions of neurons. Nevertheless, the mechanisms by which TDP-43 contributes to oxidative stress and iron accumulation in the central nervous system remain elusive. In this study, we aimed to investigate whether <em>Fth1</em> mRNA is a target transported to the axon by TDP-43 using biophysical and biochemical analyses. Our results revealed <em>Fth1</em> mRNA as a target mRNA transported to axons by TDP-43. Moreover, we demonstrated that TDP-43 regulates iron homeostasis and oxidative stress in neurons via <em>Fth1</em> mRNA transport to the axons, possibly followed by a local translation of the ferritin heavy chain in the axons. This study suggests that TDP-43 plays an important role in preventing iron-mediated oxidative stress in neurons, with its loss contributing to ALS pathogenesis.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"184 ","pages":"Article 105934"},"PeriodicalIF":4.4,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997946","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":"Neurosteroids and Translocator Protein (TSPO) in neuroinflammation","authors":"Elisa Angeloni,&nbsp;Lorenzo Germelli,&nbsp;Barbara Costa,&nbsp;Claudia Martini,&nbsp;Eleonora Da Pozzo","doi":"10.1016/j.neuint.2024.105916","DOIUrl":"10.1016/j.neuint.2024.105916","url":null,"abstract":"<div><div>Neurosteroids have a crucial role in physiological intrinsic regulations of the Central Nervous System functions. They are derived from peripheral steroidogenic sources and from the <em>d</em><em>e novo</em> neurosteroidogenic capacity of brain cells. Significant alterations of neurosteroid levels have been frequently observed in neuroinflammation and neurodegenerative diseases. Such level fluctuations may be useful for both diagnosis and treatment of these pathological conditions. Beyond steroid administration, enhancing the endogenous production by Translocator Protein (TSPO) targeting has been proposed to restore these altered pathological levels. However, the neurosteroid quantification and the prediction of their final effects are often troublesome, sometimes controversial and context dependent, due to the complexity of neurosteroid biosynthetic pathway and to the low produced amounts. The aim of this review is to report recent advances, and technical limitations, in neurosteroid-related strategies against neuroinflammation.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105916"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833576","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}