Neurotherapeutics最新文献_第7页

Targeting the Hippo pathway in Schwann cells ameliorates peripheral nerve degeneration via a polypharmacological mechanism 以许旺细胞中的希波通路为靶点，通过多药理学机制改善周围神经变性。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-01 DOI: 10.1016/j.neurot.2024.e00458

Hyung-Joo Chung , Thy N.C. Nguyen , Ji Won Lee , Youngbuhm Huh , Seungbeom Ko , Heejin Lim , Hyewon Seo , Young-Geun Ha , Jeong Ho Chang , Jae-Sung Woo , Ji-Joon Song , So-Woon Kim , Jin San Lee , Jung-Soon Mo , Boyoun Park , Kyung-Won Min , Je-Hyun Yoon , Min-Sik Kim , Junyang Jung , Na Young Jeong

{"title":"Targeting the Hippo pathway in Schwann cells ameliorates peripheral nerve degeneration via a polypharmacological mechanism","authors":"Hyung-Joo Chung , Thy N.C. Nguyen , Ji Won Lee , Youngbuhm Huh , Seungbeom Ko , Heejin Lim , Hyewon Seo , Young-Geun Ha , Jeong Ho Chang , Jae-Sung Woo , Ji-Joon Song , So-Woon Kim , Jin San Lee , Jung-Soon Mo , Boyoun Park , Kyung-Won Min , Je-Hyun Yoon , Min-Sik Kim , Junyang Jung , Na Young Jeong","doi":"10.1016/j.neurot.2024.e00458","DOIUrl":"10.1016/j.neurot.2024.e00458","url":null,"abstract":"<div><div>Peripheral neuropathies (PNs) are common diseases in elderly individuals characterized by Schwann cell (SC) dysfunction and irreversible Wallerian degeneration (WD). Although the molecular mechanisms of PN onset and progression have been widely studied, therapeutic opportunities remain limited. In this study, we investigated the pharmacological inhibition of Mammalian Ste20-like kinase 1/2 (MST1/2) by using its chemical inhibitor, XMU-MP-1 (XMU), against WD. XMU treatment suppressed the proliferation, dedifferentiation, and demyelination of SCs in models of WD <em>in vitro</em>, <em>in vivo</em>, and <em>ex vivo</em>. As a downstream mediator of canonical and noncanonical Hippo/MST1 pathway activation, the mature microRNA (miRNA) let-7b and its binding partners quaking homolog (QKI)/nucleolin (NCL) modulated miRNA-mediated silencing of genes involved in protein transport. Hence, direct phosphorylation of QKI and NCL by MST1 might be critical for WD onset and pathogenesis. Moreover, p38α/mitogen-activated protein kinase 14 (p38α) showed a strong affinity for XMU, and therefore, it may be an alternative XMU target for controlling WD in SCs. Taken together, our findings provide new insights into the Hippo/MST pathway function in PNs and suggest that XMU is a novel multitargeted therapeutic for elderly individuals with PNs.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"21 6","pages":"Article e00458"},"PeriodicalIF":5.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “Activation of Galanin receptor 1 with M617 attenuates neuronal apoptosis via ERK/GSK-3β/TIP60 pathway after subarachnoid hemorrhage in Rats” [Neurotherapeutics 18 (3) (2021) 1905–1921] 用M617激活Galanin受体1，通过ERK/GSK-3β/TIP60途径减轻大鼠蛛网膜下腔出血后神经细胞凋亡》的更正 [Neurotherapeutics 18 (3) (2021) 1905-1921]。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-01 DOI: 10.1016/j.neurot.2024.e00468

Hui Shi , Yuanjian Fang , Lei Huang , Ling Gao , Cameron Lenahan , Takeshi Okada , Zachary D. Travis , Shucai Xie , Hong Tang , Qin Lu , Rui Liu , Jiping Tang , Yuan Cheng , John H. Zhang

引用次数: 0

Neuroplasticity in the transition from acute to chronic pain 从急性疼痛到慢性疼痛转变过程中的神经可塑性。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-01 DOI: 10.1016/j.neurot.2024.e00464

Qingbiao Song , Sihan E , Zhiyu Zhang , Yingxia Liang

引用次数: 0

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-01 DOI: 10.1016/j.neurot.2024.e00447

Xiaxin Yang , Jianhang Zhang , Zhihao Wang , Zhong Yao , Xue Yang , Xingbang Wang , Xiuhe Zhao , Shuo Xu

{"title":"Mitochondria-related HSDL2 is a potential biomarker in temporal lobe epilepsy by modulating astrocytic lipid metabolism","authors":"Xiaxin Yang , Jianhang Zhang , Zhihao Wang , Zhong Yao , Xue Yang , Xingbang Wang , Xiuhe Zhao , Shuo Xu","doi":"10.1016/j.neurot.2024.e00447","DOIUrl":"10.1016/j.neurot.2024.e00447","url":null,"abstract":"<div><div>Temporal lobe epilepsy (TLE) is the most prevalent type of focal epilepsy in adults. While comprehensive bioinformatics analyses have facilitated the identification of novel biomarkers in animal models, similar efforts are limited for TLE patients. In the current study, a comprehensive analysis using human transcriptomics datasets GSE205661, GSE190451, and GSE186334 was conducted to reveal differentially expressed genes related to mitochondria (Mito-DEGs). Protein-protein interaction (PPI) network and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to identify hub genes. Additional GSE127871 and GSE255223 were utilized to establish the association with hippocampal sclerosis (HS) and seizure frequency, respectively. Single-cell RNA analysis, functional investigation, and clinical verification were conducted. Herein, we reported that the Mito-DEGs in human TLE were significantly enriched in metabolic processes. Through PPI and LASSO analysis, HSDL2 was identified as the hub gene, of which diagnostic potential was further confirmed using independent datasets, animal models, and clinical validation. Subsequent single-cell and functional analyses revealed that HSDL2 expression was enriched and upregulated in response to excessive lipid accumulation in astrocytes. Additionally, the diagnostic efficiency of blood HSDL2 was verified in Qilu cohort. Together, our findings highlight the translational potential of HSDL2 as a biomarker and provide a novel therapeutic perspective for human TLE.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"21 6","pages":"Article e00447"},"PeriodicalIF":5.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Life history of a brain autoreactive T cell: From thymus through intestine to blood-brain barrier and brain lesion 脑自反应 T 细胞的生命史：从胸腺到肠道，再到血脑屏障和脑损伤。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-01 DOI: 10.1016/j.neurot.2024.e00442

Naoto Kawakami , Hartmut Wekerle

引用次数: 0

Corrigendum to “A real-time neurophysiologic stress test for the aging brain: Novel perioperative and ICU applications of EEG in older surgical patients” Neurotherapeutics 20 (4) (2023) 975–1000 老化大脑的实时神经生理学压力测试：神经治疗学 20 (4) (2023) 975-1000。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-01 DOI: 10.1016/j.neurot.2024.e00473

Miles Berger , David Ryu , Melody Reese , Steven McGuigan , Lisbeth A. Evered , Catherine C. Price , David A. Scott , M. Brandon Westover , Roderic Eckenhoff , Laura Bonanni , Aoife Sweeney , Claudio Babiloni

引用次数: 0

Extracellular vesicles from mesenchymal stem cells alter gut microbiota and improve neuroinflammation and motor impairment in rats with mild liver damage 间充质干细胞的细胞外囊泡能改变肠道微生物群，改善轻度肝损伤大鼠的神经炎症和运动障碍。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-01 DOI: 10.1016/j.neurot.2024.e00445

Gergana Mincheva , Vicente Felipo , Victoria Moreno-Manzano , Alfonso Benítez-Páez , Marta Llansola

{"title":"Extracellular vesicles from mesenchymal stem cells alter gut microbiota and improve neuroinflammation and motor impairment in rats with mild liver damage","authors":"Gergana Mincheva , Vicente Felipo , Victoria Moreno-Manzano , Alfonso Benítez-Páez , Marta Llansola","doi":"10.1016/j.neurot.2024.e00445","DOIUrl":"10.1016/j.neurot.2024.e00445","url":null,"abstract":"<div><div>Gut microbiota perturbation and motor dysfunction have been reported in steatosis patients. Rats with mild liver damage (MLD) show motor dysfunction mediated by neuroinflammation and altered GABAergic neurotransmission in the cerebellum. The extracellular vesicles (EV) from mesenchymal stem cells (MSC) have emerged as a promising therapeutic proxy whose molecular basis relies partly upon TGFβ action. This study aimed to assess if MSC-EVs improve motor dysfunction in rats with mild liver damage and analyze underlying mechanisms, including the role of TGFβ, cerebellar neuroinflammation and gut microbiota. MLD in rats was induced by carbon tetrachloride administration and EVs from normal (C-EVs) or TGFβ-siRNA treated MSCs (T-EV) were injected. Motor coordination, locomotor gait, neuroinflammation and TNF-α-activated pathways modulating GABAergic neurotransmission in the cerebellum, microbiota composition in feces and microbial-derived metabolites in plasma were analyzed. C-EVs reduced glial and TNFα-P2X4-BDNF-TrkB pathway activation restoring GABAergic neurotransmission in the cerebellum and improving motor coordination and all the altered gait parameters. T-EVs also improved motor coordination and some gait parameters, but the mechanisms involved differed from those of C-EVs. MLD rats showed increased content of some <em>Bacteroides</em> species in feces, correlating with decreased kynurenine aside from motor alterations. These alterations were all normalized by C-EVs, whereas T-EVs only restored kynurenine levels. Our results support the value of MSC-EVs on improving motor dysfunction in MLD and unveil a possible mechanism by which altered microbiota may contribute to neuroinflammation and motor impairment. Some of the underlying mechanisms are TGFβ-dependent.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"21 6","pages":"Article e00445"},"PeriodicalIF":5.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The brain pathobiome in Alzheimer's disease 阿尔茨海默病的大脑病理生物群。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-01 DOI: 10.1016/j.neurot.2024.e00475

Nanda Kumar Navalpur Shanmugam , William A. Eimer , Deepak K. Vijaya Kumar , Rudolph E. Tanzi

引用次数: 0

Microbiome and micronutrient in ALS: From novel mechanisms to new treatments ALS 中的微生物组和微量营养素：从新机制到新疗法

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-01 DOI: 10.1016/j.neurot.2024.e00441

Jun Sun , Yongguo Zhang

{"title":"Microbiome and micronutrient in ALS: From novel mechanisms to new treatments","authors":"Jun Sun , Yongguo Zhang","doi":"10.1016/j.neurot.2024.e00441","DOIUrl":"10.1016/j.neurot.2024.e00441","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis is a neurodegenerative disorder. Despite extensive studies, it remains challenging to treat ALS. Recent ALS studies have shown dysbiosis (e.g., loss of microbial diversity and beneficial function in the gut microbiota) is correlated with intestinal inflammation and change of intestinal integrity in ALS. The novel concepts and the roles of microbiome and microbial metabolites through the gut-microbiome-neuron axis in ALS pathogenesis have been slowly recognized by the neurology research field. Here, we will discuss the recent progress of microbiome, including bacteria, fungi, and viruses, in the ALS research. We will discuss our understanding of microbial metabolites in ALS. Micronutrition refers to the intake of essential vitamins, minerals, and other micronutrients. We will summarize the literation related to micronutrition and ALS. Furthermore, we will consider the mutual interactions of microbiome and micronutrition in the ALS progression and treatment. We further propose that the mechanistic and translational studies that shift from suspension of disbelief to cogent ingenuity, and from bench study to bed-side application, should allow new strategies of diagnosis and treatment for ALS.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"21 6","pages":"Article e00441"},"PeriodicalIF":5.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preclinical study of the antimyotonic efficacy of safinamide in the myotonic mouse model 在肌强直小鼠模型中对沙芬那胺抗肌强直功效的临床前研究。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-10-01 DOI: 10.1016/j.neurot.2024.e00455

Ileana Canfora , Concetta Altamura , Jean-Francois Desaphy , Brigida Boccanegra , Silvia Vailati , Carla Caccia , Elsa Melloni , Gloria Padoani , Annamaria De Luca , Sabata Pierno

{"title":"Preclinical study of the antimyotonic efficacy of safinamide in the myotonic mouse model","authors":"Ileana Canfora , Concetta Altamura , Jean-Francois Desaphy , Brigida Boccanegra , Silvia Vailati , Carla Caccia , Elsa Melloni , Gloria Padoani , Annamaria De Luca , Sabata Pierno","doi":"10.1016/j.neurot.2024.e00455","DOIUrl":"10.1016/j.neurot.2024.e00455","url":null,"abstract":"<div><div>Mexiletine is the first choice drug in the treatment of non-dystrophic myotonias. However, 30% of patients experience little benefit from mexiletine due to poor tolerability, contraindications and limited efficacy likely based on pharmacogenetic profile. Safinamide inhibits neuronal voltage-gated sodium and calcium channels and shows anticonvulsant activity, in addition to a reversible monoamine oxidase-B inhibition. We evaluated the preclinical effects of safinamide in an animal model of Myotonia Congenita, the ADR (arrested development of righting response) mouse. In vitro studies were performed using the two intracellular microelectrodes technique in current clamp mode. We analyzed sarcolemma excitability in skeletal muscle fibers isolated from male and female ADR (adr/adr) and from Wild-Type (wt/wt) mice, before and after the application of safinamide and the reference compound mexiletine. In ADR mice, the maximum number of action potentials (N-spikes) elicited by a fixed current is higher with respect to that of WT mice. Myotonic muscles show an involuntary firing of action potential called after-discharges. A more potent activity of safinamide compared to mexiletine has been demonstrated in reducing N-spikes and the after-discharges in myotonic muscle fibers. The time of righting reflex (TRR) before and after administration of safinamide and mexiletine was evaluated in vivo in ADR mice. Safinamide was able to reduce the TRR in ADR mice to a greater extent than mexiletine. In conclusion, safinamide counteracted the abnormal muscle hyperexcitability in myotonic mice both in vitro and in vivo suggesting it as an effective drug to be indicated in Myotonia Congenita.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"21 6","pages":"Article e00455"},"PeriodicalIF":5.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0