Neurochemistry international最新文献_第7页

Therapeutic potential of cell-permeable PEP-1-Srxn1 in mitigating oxidative and ischemic damage in the hippocampus 细胞渗透性PEP-1-Srxn1在减轻海马氧化和缺血性损伤中的治疗潜力

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-05-07 DOI: 10.1016/j.neuint.2025.105988

Kyu Ri Hahn , Hyun Jung Kwon , Seung Myung Moon , Woosuk Kim , In Koo Hwang , Dae Won Kim , Dae Young Yoo

{"title":"Therapeutic potential of cell-permeable PEP-1-Srxn1 in mitigating oxidative and ischemic damage in the hippocampus","authors":"Kyu Ri Hahn , Hyun Jung Kwon , Seung Myung Moon , Woosuk Kim , In Koo Hwang , Dae Won Kim , Dae Young Yoo","doi":"10.1016/j.neuint.2025.105988","DOIUrl":"10.1016/j.neuint.2025.105988","url":null,"abstract":"<div><div>In the present study, we validated the neuroprotective effects of sulfiredoxin 1 (Srxn1) against oxidative damage in HT22 cells and ischemic damage in gerbil hippocampus. To efficiently deliver Srxn1 protein into cells or the hippocampus, a PEP-1-Srxn1 fusion protein was synthesized, and efficient delivery was visualized in HT22 mouse hippocampal neuronal cells. PEP-1-Srxn1 was delivered to HT22 cells in a concentration- and incubation time-dependent manner and showed significantly higher levels at 36 h after incubation for 1 h. Morphologically, the delivered protein was localized in the cytoplasm of HT22 cells. In addition, PEP-1-Srxn1 treatment significantly ameliorated formation of reactive oxygen species, DNA fragmentation, and cell death in HT22 cells induced by treatment with 100 μM H<sub>2</sub>O<sub>2</sub>. In gerbils, PEP-1-Srxn1 treatment significantly alleviated transient ischemia-induced forebrain hyperactivity 1 d after ischemia and memory deficits 4 d after ischemia. Neuroprotective effects were confirmed by morphological analysis of the hippocampal CA1 region 4 or 10 d after ischemia. Treatment with PEP-1-Srxn1 significantly ameliorated the formation of reactive oxygen species and lipid peroxidation in the hippocampus during the early stages (3–12 h) of ischemia. In addition, treatment with PEP-1-Srxn1 alleviated the ischemia-induced reduction of glutathione levels in the hippocampus. PEP-1-Srxn1 also decreased ischemia-induced microglial activation and pro-inflammatory cytokine release in the hippocampus. These results suggest that PEP-1-Srxn1 is a potential therapeutic agent for reducing neuronal damage induced by oxidative or ischemic damage.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105988"},"PeriodicalIF":4.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941282","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}

引用次数: 0

The effect of Fibulin-5 on early brain injury after subarachnoid hemorrhage in mice 纤维蛋白-5对小鼠蛛网膜下腔出血后早期脑损伤的影响

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-05-06 DOI: 10.1016/j.neuint.2025.105989

Yume Suzuki, Mai Nampei, Fumihiro Kawakita, Hiroki Oinaka, Hideki Nakajima, Hidenori Suzuki

{"title":"The effect of Fibulin-5 on early brain injury after subarachnoid hemorrhage in mice","authors":"Yume Suzuki, Mai Nampei, Fumihiro Kawakita, Hiroki Oinaka, Hideki Nakajima, Hidenori Suzuki","doi":"10.1016/j.neuint.2025.105989","DOIUrl":"10.1016/j.neuint.2025.105989","url":null,"abstract":"<div><div>Early brain injury (EBI) is an important cause that determines outcomes after aneurysmal subarachnoid hemorrhage (SAH). Our recent clinical study reported that a high concentration of plasma fibulin-5 (FBLN5), one of matricellular proteins, was associated with poor outcomes after SAH. The aim of this study was to investigate whether and how FBLN5 was associated with EBI during an acute phase of SAH in mice. C57BL/6 male mice underwent sham or filament perforation SAH modeling, and vehicle or four dosages (0.001, 0.01, 0.1, and 1 μg) of short or long recombinant FBLN5 (rFBLN5) were randomly administrated by an intracerebroventricular injection. Neurobehavioral test, measurements of brain water content, immunohistochemical staining, and Western blotting were performed to evaluate EBI 24 h after SAH. Short rFBLN5 had no significant effects on EBI, but administration of long rFBLN5 containing an arginine-glycine-aspartic acid motif improved neurobehavior functions depending on the dosages, without affecting brain edema. Administration of long rFBLN5 also reduced cleaved caspase-3-dependent neuronal apoptosis, associated with the inhibition of post-SAH upregulation of transforming growth factor-β1, but no significant changes in the expression level of Smad 2/3, mitogen-activated protein kinases, and another matricellular protein tenascin-C. Although further research is required to clarify the detailed mechanism, this study demonstrated for the first time that FBLN5 played a protective role against neuronal apoptosis in an acute phase of experimental SAH.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105989"},"PeriodicalIF":4.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924270","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}

引用次数: 0

Sulforaphane prevents cognitive decline and mitochondrial failure induced by hippocampal expression of caspase-3 cleaved tau 萝卜硫素可预防海马表达caspase-3切割tau蛋白引起的认知能力下降和线粒体衰竭

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-05-06 DOI: 10.1016/j.neuint.2025.105991

Francisca Villavicencio-Tejo , Margrethe A. Olesen , Estibaliz Ampuero , Rodrigo A. Quintanilla

{"title":"Sulforaphane prevents cognitive decline and mitochondrial failure induced by hippocampal expression of caspase-3 cleaved tau","authors":"Francisca Villavicencio-Tejo , Margrethe A. Olesen , Estibaliz Ampuero , Rodrigo A. Quintanilla","doi":"10.1016/j.neuint.2025.105991","DOIUrl":"10.1016/j.neuint.2025.105991","url":null,"abstract":"<div><div>Caspase-3 cleaved tau (truncated tau) is a pathological modification in tau protein that contributes to neurofibrillary tangle formation (NFTs) and neurodegeneration in AD. Our previous studies indicate that truncated tau affects mitochondrial health, synaptic plasticity, and cognitive performance. Therefore, we studied the effects of sulforaphane (SFN), a natural compound activator of the NRF2 antioxidant pathway present in vegetables and sprouts, on neurodegeneration and cognitive decline induced by truncated tau expression <em>in vivo</em>.</div><div>We induced a 2-month hippocampal expression of GFP, full-length (AAV-Syn-GFP-T4) and truncated tau (AAV-Syn-GFP-T4C3) using a stereotaxic injection of adeno-associated-virus-9 (AAV9) linked to GFP and a synapsin neuronal promoter in tau (−/−) mice. Hippocampal tau-expressing mice were treated with SFN, and their cognitive performance (NOR, NOL, and Barnes maze tests) and hippocampal mitochondrial function were analyzed.</div><div>Interestingly, hippocampal truncated tau expression significantly affected cognitive and memory abilities, accompanied by increased ROS and severe mitochondrial dysfunction (depolarization, ATP loss, dynamics de-regulation). Notably, the treatment with SFN (50 mg/kg/day, i.p., two weeks) prevented cognitive impairment and reduced mitochondrial bioenergetics and dynamics defects induced by hippocampal truncated tau expression.</div><div>These findings suggest a potential role of SFN in ameliorating cognitive loss and mitochondrial impairment promoted by tau pathology in neurological disorders (NDs).</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105991"},"PeriodicalIF":4.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918533","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}

引用次数: 0

Effects of maternal depression and antidepressant treatment on neurotransmitters, brain regions, and mitochondrial function in rat dams 母亲抑郁和抗抑郁治疗对大鼠神经递质、脑区和线粒体功能的影响

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-05-02 DOI: 10.1016/j.neuint.2025.105981

Marianna Maková , Svatava Kašparová , Ladislav Bačiak , Daniel Gogola , Zuzana Sumbalová , Ingrid Brucknerová , Stanislava Bukatová , Michal Dubovický

{"title":"Effects of maternal depression and antidepressant treatment on neurotransmitters, brain regions, and mitochondrial function in rat dams","authors":"Marianna Maková , Svatava Kašparová , Ladislav Bačiak , Daniel Gogola , Zuzana Sumbalová , Ingrid Brucknerová , Stanislava Bukatová , Michal Dubovický","doi":"10.1016/j.neuint.2025.105981","DOIUrl":"10.1016/j.neuint.2025.105981","url":null,"abstract":"<div><div>Increasing evidence suggests that mothers experience stress before or during pregnancy, which can significantly impact their GABAergic system and lead to amygdala hyperactivity. While animal models are expected to reflect the above findings in humans, the current knowledge on the effects of chronic unpredictable mild stress (CUMS) in rat dams remains insufficient. Therefore, the objective of this study was to investigate the structural and neurochemical alterations in the dorsal hippocampus, specifically gamma-aminobutyric acid (GABA) and glutamate (Glu) relative to total creatine (tCr), induced by the CUMS and the effects of antidepressant mirtazapine (MIR) treatment. Magnetic resonance imaging and proton localized magnetic resonance spectroscopy were used in rat dams at two time points to assess the reversibility of these alterations. Eight weeks post-CUMS, chronic stress induced significant alterations in hippocampal metabolism and structural changes, including lower GABA/tCr concentrations and an increased amygdala volume compared to controls. In stressed dams treated with MIR, no changes in GABA levels or amygdala volume were observed. Fourteen weeks post-CUMS, no significant changes in hippocampal neurochemistry were confirmed, while amygdala changes persisted in stressed dams. Moreover, significant time-dependent changes were observed in the amygdala and hypothalamus in the control group with MIR. Interestingly, high-resolution respirometry was performed to assess brain mitochondrial function, revealing only changes in this group. Based on these findings, we confirmed the reversibility of metabolite. Furthermore, MIR has demonstrated potential in regulating neurotransmitter levels and protecting amygdala volume after stress; however, further research is needed to fully understand its therapeutic effects.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105981"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935377","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}

引用次数: 0

Corrigendum to “Supplementation with g-glutamylcysteine (γ-GC) lessens oxidative stress, brain inflammation and amyloid pathology and improves spatial memory in a murine model of AD” [Neurochem. Int. 144 (2021) 104931] “补充g-谷氨酰半胱氨酸（γ-GC）可以减轻AD小鼠模型中的氧化应激、脑炎症和淀粉样蛋白病理，并改善空间记忆”[Neurochem]的更正。Int. 144(2021) 104931]。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-04-30 DOI: 10.1016/j.neuint.2025.105978

Yue Liu , Zheng Chen , Ben Li , Hua Yao , Martin Zarka , Jeffrey Welch , Perminder Sachdev , Wallace Bridge , Nady Braidy

引用次数: 0

Truncation mutation of CHMP2B disrupts late endosome function but reduces TDP-43 aggregation through HSP70 upregulation CHMP2B的截断突变破坏了内核体的晚期功能，但通过HSP70的上调减少了TDP-43的聚集

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-04-30 DOI: 10.1016/j.neuint.2025.105982

Yohei Iguchi , Yuhei Takahashi , Jiayi Li , Yoshinobu Amakusa , Yu Kawakami , Takashi Yoshimura , Ryo Chikuchi , Madoka Iida , Satoshi Yokoi , Masahisa Katsuno

{"title":"Truncation mutation of CHMP2B disrupts late endosome function but reduces TDP-43 aggregation through HSP70 upregulation","authors":"Yohei Iguchi , Yuhei Takahashi , Jiayi Li , Yoshinobu Amakusa , Yu Kawakami , Takashi Yoshimura , Ryo Chikuchi , Madoka Iida , Satoshi Yokoi , Masahisa Katsuno","doi":"10.1016/j.neuint.2025.105982","DOIUrl":"10.1016/j.neuint.2025.105982","url":null,"abstract":"<div><div>TAR DNA-binding protein 43 (TDP-43)-positive cytoplasmic aggregation is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). This aggregation contributes substantially to the neurodegeneration of ALS and FTLD. The endosome, a key component of membrane trafficking in eukaryotic cells and is involved in the autophagy–lysosome pathway. Endosome-related genes such as <em>CHMP2B</em>, <em>Alsin</em>, and <em>TMEM106B,</em> are either causative or act as genetic modifiers in ALS and FTLD. However, the association between endosomal functions and TDP-43 aggregations remain poorly understood. The C-terminal truncation mutation <em>CHMP2B</em>, which causes frontotemporal dementia associated with chromosome 3 (FTD3), disrupts late endosome (LE)–lysosomes fusion. Nevertheless, FTD3 does not induce TDP-43 pathology. In this study, we showed that <em>CHMP2B</em> mutation-induced LE dysfunction promotes TDP-43 aggregate degradation through enhanced recruitment to juxtanuclear quality control compartments. Transcriptomic analysis revealed that <em>CHMP2B</em><sup><em>intron5</em></sup> overexpression upregulates HSP70 expression. New insights into the connection between <em>CMHP2B</em> and HSP70 as well as the role of HSP70-mediated membrane trafficking in TDP-43 aggregation, offer a valuable understanding of the disease mechanism of ALS and FTLD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105982"},"PeriodicalIF":4.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904206","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}

引用次数: 0

RNA sequencing analysis identifies sex differences in transcriptional signatures in the dorsal striatum of female and male rats after withdrawal from methamphetamine self-administration RNA测序分析确定了雌性和雄性大鼠在停止自我给药后背纹状体转录特征的性别差异

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-04-23 DOI: 10.1016/j.neuint.2025.105980

Vaibhav V. Gujar , Atul P. Daiwile , Vikrant Palande , Jean Lud Cadet

{"title":"RNA sequencing analysis identifies sex differences in transcriptional signatures in the dorsal striatum of female and male rats after withdrawal from methamphetamine self-administration","authors":"Vaibhav V. Gujar , Atul P. Daiwile , Vikrant Palande , Jean Lud Cadet","doi":"10.1016/j.neuint.2025.105980","DOIUrl":"10.1016/j.neuint.2025.105980","url":null,"abstract":"<div><div>Significant methamphetamine (METH)-induced behavioral differences exist between the two sexes of humans and other animals. These dissimilarities may be related to sexual dimorphism in baseline molecular and biochemical mechanisms in brain reward neuroanatomical pathways. As a first step towards identifying sex-based differences in methamphetamine-induced transcriptional signatures, we used RNA sequencing analysis to measure genome-wide changes in gene expression in the dorsal striatum of rats that had self-administered METH. We trained rats to self-administer METH (0.1 mg/kg/infusion, i.v.) using two 3-hr daily sessions (with 30 min time out between sessions) for 20 days. Control rats self-administered saline under similar conditions. This was followed by drug seeking tests on withdrawal days 3 (WD3) and 30 (WD30). Behavioral results show that male rats took more METH than female rats. In both male and female rats, some animals escalated (high-takers) whereas others did not escalate (low-takers) their METH intake during the behavioral experiment. Rats were euthanized 24 h after the second drug seeking test. RNA was extracted from the dorsal striatum (dSTR) and used in RNA sequencing analysis. The data identified substantial baseline differences in gene expression between female and male control rats. In addition, METH use and withdrawal were associated with significant sex-related differences in changes in striatal gene expression, with minimal overlaps of altered mRNAs. Thus, the present results provide further supporting evidence for sexually dimorphic responses to METH exposure. These observations support the notion of sex-specific approaches to the treatment of patients who suffer from METH use disorder.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105980"},"PeriodicalIF":4.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887114","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}

引用次数: 0

Non-canonical STAT3 pathway induces alterations of mitochondrial dynamic proteins in the hippocampus of an LPS-induced murine neuroinflammation model 非规范STAT3通路诱导lps诱导的小鼠神经炎症模型海马线粒体动态蛋白的改变

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-04-08 DOI: 10.1016/j.neuint.2025.105979

Périne Millot , Laurine Duquesne , Carine San , Baptiste Porte , Claire Pujol , Benoit Hosten , Jacques Hugon , Claire Paquet , François Mouton-Liger

{"title":"Non-canonical STAT3 pathway induces alterations of mitochondrial dynamic proteins in the hippocampus of an LPS-induced murine neuroinflammation model","authors":"Périne Millot , Laurine Duquesne , Carine San , Baptiste Porte , Claire Pujol , Benoit Hosten , Jacques Hugon , Claire Paquet , François Mouton-Liger","doi":"10.1016/j.neuint.2025.105979","DOIUrl":"10.1016/j.neuint.2025.105979","url":null,"abstract":"<div><div>The activation of STAT3 is a crossroads of cellular regulation, induced in its canonical pathway by phosphorylation on a critical tyrosine residue (Y705). The existence of a STAT3 non-canonical signaling mechanisms, induced by phosphorylation at serine 727 (S727), has been recently identified in vitro. After cytoplasmic activation, non-canonical STAT3 could move to the level of mitochondria-endoplasmic reticulum contacts (MERCs).</div><div>We have previously shown that LPS injections in mouse model induce STAT3 canonical pathway, leading to its nuclear translocation and to neuroinflammation. However, the effects of LPS on activation of the non-canonical pathway and its consequences on protein complexes of MERCs remain to be determined. In an <em>in vivo</em> LPS mouse model, we found that systemic inflammation induces in hippocampus the non-canonical STAT3 pathway. LPS-induced STAT3 affects specifically MERC protein BAP31, and that of a mitochondrial membrane protein known to interact with it, TOM40. These findings shed light on the role of STAT3 on mitochondrial – endoplasmic reticulum interaction under inflammatory conditions, offering new perspectives for targeting mitochondrial function and STAT3 activation in disease contexts.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105979"},"PeriodicalIF":4.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815987","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}

引用次数: 0

Illustrating the distribution and metabolic regulatory effects of nuciferine by mass spectrometry imaging and spatial metabolomics 利用质谱成像和空间代谢组学技术阐明了灯叶碱的分布和代谢调节作用

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-04-07 DOI: 10.1016/j.neuint.2025.105977

Guangyuan Liu , Yiying Wu , Liangyu Pan , Qian Wang , Yuyu Zhang , Jingwen Yan , Panpan Zhang , Wei Zhang , Dezhi Kong

{"title":"Illustrating the distribution and metabolic regulatory effects of nuciferine by mass spectrometry imaging and spatial metabolomics","authors":"Guangyuan Liu , Yiying Wu , Liangyu Pan , Qian Wang , Yuyu Zhang , Jingwen Yan , Panpan Zhang , Wei Zhang , Dezhi Kong","doi":"10.1016/j.neuint.2025.105977","DOIUrl":"10.1016/j.neuint.2025.105977","url":null,"abstract":"<div><div>Nuciferine has been widely used in traditional Chinese medicine compound preparations and natural edible resources. Most current studies have concentrated on its lipid-lowering and weight-loss effects, while relatively few have explored its impact on central nervous system disorders. To investigate the effects of nuciferine on the nervous system and its potential pharmacological mechanisms, we mapped the distribution of nuciferine and its key metabolites in brain microregions and major organs of mice using air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). Nuciferine was found to be distributed throughout the brain, particularly in the prefrontal cortex and hippocampus. Additionally, nuciferine was detected in several peripheral organs, including the heart, liver, kidneys, and spleen. We also identified the distribution of a major demethylated metabolite (M1), which correlated with the localization of the CYP1A2 enzyme. Metabolomic analysis revealed that nuciferine significantly alters purine metabolism, specifically increasing adenosine levels while decreasing xanthine and hypoxanthine. This metabolic shift suggests a potential enhancement of neuroinhibitory effects, contributing to nuciferine's sedative, hypnotic, and analgesic properties. These findings provide novel insights into the neuropharmacological mechanisms of nuciferine.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105977"},"PeriodicalIF":4.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823811","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}

引用次数: 0

Mechanism of Tau protein incorporation into exosomes via cooperative recognition of KFERQ-like motifs by LAMP2A and HSP70 通过LAMP2A和HSP70共同识别kferq样基序，Tau蛋白进入外泌体的机制。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-04-03 DOI: 10.1016/j.neuint.2025.105976

Shan Xu , Kangyan Liu , Shiyan Qian , Jingying Wu , Jialing Hu , Dongming Zhou , Tingting Zheng

{"title":"Mechanism of Tau protein incorporation into exosomes via cooperative recognition of KFERQ-like motifs by LAMP2A and HSP70","authors":"Shan Xu , Kangyan Liu , Shiyan Qian , Jingying Wu , Jialing Hu , Dongming Zhou , Tingting Zheng","doi":"10.1016/j.neuint.2025.105976","DOIUrl":"10.1016/j.neuint.2025.105976","url":null,"abstract":"<div><div>Aggregates of the tau protein is a well-known hallmark of Alzheimer's disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD). Tau can be propagated between nerve cells or brain areas, similar as 'seed'. As a member of small extracellular vesicles, exosomes may act as one of the most important 'seeding machines', disseminating toxic tau and phosphorylated tau proteins between cells and thereby amplifying their neurotoxic effects. Therefore, exploring the underlying mechanisms of Tau loading into exosomes is of great importance. In this study, human P301L tau transfections were established in SH-SY5Y cells (SY5Y-EGFP-TauP301L cells). The content of membrane protein LAMP2A and HSP70 proteins was significantly increased in the SY5Y-EGFP-Tau P301L cells compared to control group. Tau containing KFERQ-like motifs pentapeptide interact with LAMP2A and HSP70, forming a multi-protein complex, which can be loaded into a subpopulation of exosomes. Moreover, knockout of LAMP2A significantly reduced the content of Tau protein in exosomes obtained from SY5Y-EGFP-Tau P301L cells. Thus, exosome-mediated secretion of tau protein may depend on the formation of multi-protein (KFERQ-like motif pentapeptide in tau,LAMP2A and HSP70) complex. These findings revealed the presence of a novel mechanism by which release of tau through exosome secretion pathway and that LAMP2A may play an important role in the regulation of exosome-mediated secretion of tau, which may become a potential therapeutic target for AD or other Tauopathies.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105976"},"PeriodicalIF":4.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787642","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}

引用次数: 0