Neurotherapeutics最新文献

Hydrogen inhalation and intrathecal magnesium sulfate ameliorate ischemia by suppressing cortical spreading depolarization in a rat subarachnoid hemorrhage model. 氢吸入和鞘内硫酸镁通过抑制大鼠蛛网膜下腔出血模型皮质扩张性去极化改善缺血。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2025-05-28 DOI: 10.1016/j.neurot.2025.e00617

Toru Yoshiura, Satoko Kawauchi, Sho Nishida, Sho Sato, Daichi Hagita, Arumu Endo, Masaya Nakagawa, Takashi Fujii, Yohei Otsuka, Yumiko Mishima, Kazuya Fujii, Satoru Takeuchi, Arata Tomiyama, Terushige Toyooka, Shunichi Sato, Kojiro Wada

{"title":"Hydrogen inhalation and intrathecal magnesium sulfate ameliorate ischemia by suppressing cortical spreading depolarization in a rat subarachnoid hemorrhage model.","authors":"Toru Yoshiura, Satoko Kawauchi, Sho Nishida, Sho Sato, Daichi Hagita, Arumu Endo, Masaya Nakagawa, Takashi Fujii, Yohei Otsuka, Yumiko Mishima, Kazuya Fujii, Satoru Takeuchi, Arata Tomiyama, Terushige Toyooka, Shunichi Sato, Kojiro Wada","doi":"10.1016/j.neurot.2025.e00617","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00617","url":null,"abstract":"This study investigated whether inhaled hydrogen and intrathecal magnesium could mitigate cortical spreading depolarization and delayed cerebral ischemia in a rat model of subarachnoid hemorrhage. Adult male rats underwent subarachnoid hemorrhage induction with nitric oxide synthase inhibition and high-potassium application to elicit cortical spreading depolarization. Animals were assigned to sham, control, H2, Mg, or combined H2 and Mg treatment groups. We measured direct current potentials, cerebral blood flow, brain water content, bodyweight changes, and neurological outcomes. Compared with controls, the H2 and Mg groups had significantly reduced total depolarization and hypoperfusion times. The combined treatment produced similar benefits. H2 alone rapidly shortened depolarization duration, suggesting that it may offer neuroprotection until Mg effects fully manifest. Neither treatment altered physiological parameters, brain water content, bodyweight, or neurological deficits. These findings indicate that H2 and Mg reduce key pathophysiological processes related to early brain injury and delayed cerebral ischemia following subarachnoid hemorrhage, potentially improving outcomes by minimizing depolarization events and associated ischemia. H2 therapy may provide early protective effects before Mg exertion.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00617"},"PeriodicalIF":5.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Gut microbiota mediates semaglutide attenuation of diabetes-associated cognitive decline. 肠道微生物群介导糖尿病相关认知衰退的半聚脲衰减。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2025-05-23 DOI: 10.1016/j.neurot.2025.e00615

Liqin Qi, Huimin Kang, Feihui Zeng, Menglan Zhan, Cuihua Huang, Qintao Huang, Lijing Lin, Guanlian He, Xiaoying Liu, Xiaohong Liu, Libin Liu

{"title":"Gut microbiota mediates semaglutide attenuation of diabetes-associated cognitive decline.","authors":"Liqin Qi, Huimin Kang, Feihui Zeng, Menglan Zhan, Cuihua Huang, Qintao Huang, Lijing Lin, Guanlian He, Xiaoying Liu, Xiaohong Liu, Libin Liu","doi":"10.1016/j.neurot.2025.e00615","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00615","url":null,"abstract":"Diabetes-associated cognitive decline (DACD), characterized by cognitive impairment, is a serious complication of diabetes mellitus (DM). Research has shown that semaglutide, a novel glucagon-like peptide-1 receptor agonist, has neurotrophic and neuroprotective properties. However, a comprehensive understanding of the specific effects and underlying mechanisms of semaglutide treatment in patients with DACD remains lacking. In this study, we evaluated the potential of semaglutide to alleviate DACD in mice with DM. Eight-week-old mice fed a high-fat diet with streptozotocin-induced DM were subcutaneously injected with semaglutide (30 nmol/kg qd) for 12 weeks. Semaglutide administration significantly alleviated cognitive impairment, inhibited hippocampal neuron loss, improved the hippocampal synaptic ultrastructure, and effectively mitigated neuroinflammation. Furthermore, semaglutide treatment increased the relative abundances of g_Alistipes, g_norank_f_Eubacterium_coprostanoligenes, g_Bacteroides, and g_Parabacteroides, while decreasing the relative abundances of g_ faecalibaculum, g_Colodertribacter, g_GCA-900066575, g_Erysipelatoclostridium, and g_norank_f_Lachnospiraceae. Semaglutide also induced alterations in fecal and serum metabolites, as well as transcriptomic changes in brain tissue, with significant common enrichment in neuroactive ligand-receptor interactions. Furthermore, strong correlations were observed among semaglutide-affected genes, metabolites, and microbiota, as assessed by correlation analysis and integrative modeling. In conclusion, these findings suggest a correlation between the protective effects of semaglutide against DACD and the microbiota-gut-brain axis.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00615"},"PeriodicalIF":5.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Systemic nimodipine affects pericyte calcium signaling, resting hemodynamics and neurovascular coupling in healthy mouse brain. 全身尼莫地平影响健康小鼠脑周细胞钙信号、静息血流动力学和神经血管耦合。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2025-05-21 DOI: 10.1016/j.neurot.2025.e00614

Jessica Meza-Resillas, Finnegan O'Hara, Syed Kaushik, Michael J Stobart, Noushin Ahmadpour, Meher Kantroo, John Del Rosario, Megan C Rodriguez, Dmytro Koval, Chaim Glück, Bruno Weber, Jillian L Stobart

{"title":"Systemic nimodipine affects pericyte calcium signaling, resting hemodynamics and neurovascular coupling in healthy mouse brain.","authors":"Jessica Meza-Resillas, Finnegan O'Hara, Syed Kaushik, Michael J Stobart, Noushin Ahmadpour, Meher Kantroo, John Del Rosario, Megan C Rodriguez, Dmytro Koval, Chaim Glück, Bruno Weber, Jillian L Stobart","doi":"10.1016/j.neurot.2025.e00614","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00614","url":null,"abstract":"Nimodipine is a L-type voltage gated calcium channel blocker commonly given to patients after a sub-arachnoid hemorrhage. It is known to dilate cerebral arteries and affect brain pericytes that express voltage gated calcium channels. Here, we systemically administered nimodipine (1 mg/kg; i.p.) and measured brain pericyte calcium transients and single-vessel hemodynamics in the brains of mice by two-photon microscopy. We find that nimodipine reduces calcium transients in all types of pericytes, from ensheathing to thin-strand cells, at different locations in the vascular network. This induces local vasodilation of vessels closer to penetrating arterioles but decreases blood cell velocity. These vascular consequences are due to systemic nimodipine effects because direct brain application of nimodipine caused blood cell velocity to increase. Nimodipine treatment also reduced further dilation during neurovascular coupling throughout the vascular network. Overall, this suggests that nimodipine can change cerebrovascular hemodynamics by altering pericyte physiology and these are important considerations for the clinical use of this drug.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00614"},"PeriodicalIF":5.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Lysophosphatidic acid receptor 5 in insular cortex as a potential analgesic target in neuropathic pain. 岛叶皮质溶血磷脂酸受体5作为神经性疼痛的潜在镇痛靶点。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2025-05-20 DOI: 10.1016/j.neurot.2025.e00609

Bing Wang, Xiaozhou Feng, Kristen Woodhouse, Dilip Sharma, Xianglei Meng, Huijie Shang, Huijuan Hu, Dehui Zhang, Yanan Zhang, Jun-Xu Li, Yuan-Xiang Tao

{"title":"Lysophosphatidic acid receptor 5 in insular cortex as a potential analgesic target in neuropathic pain.","authors":"Bing Wang, Xiaozhou Feng, Kristen Woodhouse, Dilip Sharma, Xianglei Meng, Huijie Shang, Huijuan Hu, Dehui Zhang, Yanan Zhang, Jun-Xu Li, Yuan-Xiang Tao","doi":"10.1016/j.neurot.2025.e00609","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00609","url":null,"abstract":"Neuropathic pain remains a significant clinical challenge and existing treatments have limited efficacy and often over rely on opioids. Pharmacological inhibition and genetic knockout of lysophosphatidic acid receptor 5 (LPA5) lead to an analgesic effect on nerve injury-induced nociceptive hypersensitivity in rodents. However, the specific pain-associated regions where LPA5 is required for neuropathic pain remain unidentified. Here, we demonstrate a site-specific increase in the levels of Lpa5 mRNA and LPA5 protein in the contralateral insular cortex and hippocampus 3-14 days after chronic constriction injury (CCI) of the unilateral sciatic nerve in mice. Blocking this time-dependent increase through microinjection of adeno-associated virus 5 (AAV5) expressing Lpa5 shRNA (AAV5-LPA5 shRNA) into insular cortex mitigated CCI-induced development of nociceptive hypersensitivities. This effect was not seen after microinjection of AAV5-LPA5 shRNA into the hippocampus. Mimicking this increase through microinjection of AAV5 expressing full-length Lpa5 mRNA into the insular cortex augmented responses to mechanical, heat and cold stimuli and induced ongoing pain in naïve mice. Moreover, systemic administration of selective LPA5 antagonist RLPA-76 alleviated CCI-induced mechanical allodynia and heat hyperalgesia. All treated mice displayed normal locomotor activities. Altogether, these findings suggest that LPA5 in the insular cortex plays a critical role in neuropathic pain genesis and support LPA5 as a potential target for neuropathic pain treatment.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00609"},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Discovery of an APP-selective BACE1 inhibitor for Alzheimer's disease. app选择性BACE1抑制剂治疗阿尔茨海默病的发现。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2025-05-20 DOI: 10.1016/j.neurot.2025.e00610

Jesus Campagna, Barbara Jagodzinska, Dongwook Wi, Chunni Zhu, Jessica Lee, Whitaker Cohn, Michael Jun, Chris Elias, Samar Padder, Olivier Descamps, Clare Peters-Libeu, Qiang Zhang, Olivia Gorostiza, Karen Poksay, Patricia Spilman, Dale Bredesen, Varghese John

{"title":"Discovery of an APP-selective BACE1 inhibitor for Alzheimer's disease.","authors":"Jesus Campagna, Barbara Jagodzinska, Dongwook Wi, Chunni Zhu, Jessica Lee, Whitaker Cohn, Michael Jun, Chris Elias, Samar Padder, Olivier Descamps, Clare Peters-Libeu, Qiang Zhang, Olivia Gorostiza, Karen Poksay, Patricia Spilman, Dale Bredesen, Varghese John","doi":"10.1016/j.neurot.2025.e00610","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00610","url":null,"abstract":"Inhibition of amyloid precursor protein (APP) beta-site cleaving enzyme 1 (BACE1) has been a target for Alzheimer's disease (AD) therapeutic development. Here, we report our identification of APP-selective BACE1 (ASBI) inhibitors that are selective for APP as the substrate and BACE1 as the target enzyme. A known fluoro aminohydantoin (FAH) inhibitor compound was identified by screening a compound library for inhibition of BACE1 cleavage of a maltose binding protein (MBP)-conjugated-APPC125 substrate followed by optimization and IC50 determination using the P5-P5' activity assay. Optimization of the screening hit led to candidate FAH65, which displays selectivity for inhibition of APP cleavage with little activity against other BACE1 substrates neuregulin 1 (NRG1) or p-selectin glycoprotein ligand-1 (PSGL1). FAH65 shows little inhibitory activity against other aspartyl proteases cathepsin D (Cat D) and BACE2. FAH65 reduces BACE1 cleavage products soluble APPβ (sAPPβ) and the β C-terminal fragment (βCTF), as well as amyloid-β (Aβ) 1-40 and 1-42, both in vitro in cells and in vivo in an animal model of AD. In a murine model of AD, FAH65 improved the discrimination score in the Novel Object Recognition (NOR) memory testing paradigm. The active enantiomer of racemate FAH65, FAH65E(-), displays good brain-penetrance and target engagement, meriting further pre-clinical development as an ASBI that may reduce Aβ levels and overcome the deleterious effects of the non-selective BACE1 inhibitors that have failed in the clinic. FAH65E(-) has the potential to be a first-in-class oral therapy that could be used in conjunction with an approved anti-Aβ antibody therapy for AD.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00610"},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Functional neurological disorder: Practical management. 功能性神经障碍：实际管理。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2025-05-20 DOI: 10.1016/j.neurot.2025.e00612

Barbara A Dworetzky, Gaston Baslet

引用次数: 0

Treating postextubation dysphagia after stroke with pharyngeal electrical stimulation -insights from a randomized controlled pilot trial. 咽电刺激治疗中风拔管后吞咽困难——来自一项随机对照试验的见解。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2025-05-17 DOI: 10.1016/j.neurot.2025.e00613

Sonja Suntrup-Krueger, Bendix Labeit, Jonas von Itter, Anne Jung, Inga Claus, Sigrid Ahring, Tobias Warnecke, Rainer Dziewas, Paul Muhle

{"title":"Treating postextubation dysphagia after stroke with pharyngeal electrical stimulation -insights from a randomized controlled pilot trial.","authors":"Sonja Suntrup-Krueger, Bendix Labeit, Jonas von Itter, Anne Jung, Inga Claus, Sigrid Ahring, Tobias Warnecke, Rainer Dziewas, Paul Muhle","doi":"10.1016/j.neurot.2025.e00613","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00613","url":null,"abstract":"Postextubation dysphagia is a major risk factor for extubation failure in acute stroke. Pharyngeal electrical stimulation (PES) is a novel neurostimulation technique for neurogenic dysphagia rehabilitation. We conducted a randomized controlled pilot trial evaluating PES early after extubation in acute stroke (N = 60) focusing on dysphagia recovery trajectories and related outcomes until discharge. Patients with severe postextubation dysphagia, defined as Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) score >4, received daily PES (real or sham, 10 min/day) for 3 consecutive days. By day 3, significantly fewer patients in the PES group exhibited persistent absence of spontaneous swallows (8 vs. 41 %) or pharyngeal sensory loss (4 vs. 55 %) compared to the sham group, indicating enhanced airway safety. Functional Oral Intake Scale (FOIS) score at day 3 was significantly higher in the PES group (4.1 vs 2.1 pts). FEDSS at days 5-7 and 8-10 showed a sustained treatment effect over time (2.4 vs. 3.7 pts. and 2.2 vs. 3.4 pts), resulting in better FOIS at discharge (4.7 vs. 3.5 pts.). PES shortened LOS in the intensive care unit (ICU) (3.1 vs. 8.5 days, p = 0.008) and total hospital stay (13.8 vs. 21.9 days, p = 0.004) from study inclusion. Tracheotomy rates were 13 vs. 33 % (p < 0.067). The proportion of patients still cannulated at discharge (7 vs. 10 %) and the modified Rankin Scale at discharge (3.9 vs. 4.0) were comparable. PES enhanced recovery of postextubation dysphagia, improved airway safety and shortened length of ICU and hospital stay in acute stroke.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00613"},"PeriodicalIF":5.6,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Microstructural integrity within the damaged region of the residual corticofugal projection from primary motor cortex predicts the effect of noninvasive neuromodulation targeting the spinal cord in chronic stroke. 初级运动皮层残余皮质投射损伤区域内的显微结构完整性预测了慢性卒中中针对脊髓的非侵入性神经调节的效果。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2025-05-17 DOI: 10.1016/j.neurot.2025.e00607

Michael A Urbin, Fang Liu, Chan Hong Moon

{"title":"Microstructural integrity within the damaged region of the residual corticofugal projection from primary motor cortex predicts the effect of noninvasive neuromodulation targeting the spinal cord in chronic stroke.","authors":"Michael A Urbin, Fang Liu, Chan Hong Moon","doi":"10.1016/j.neurot.2025.e00607","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00607","url":null,"abstract":"Distal limb impairment after neurological injury is largely a consequence of damage to descending tracts that structurally and functionally connect cortical motor areas with spinal motor neuron pools. Noninvasive neuromodulation strategies that aim to enhance cortico-spinal connectivity via spike timing-dependent mechanisms in the spinal cord rely on transmission of descending volleys across the residual tract. Whether variation in the aftereffects of noninvasive neuromodulation depends on the overall volume or microstructural integrity of fibers that survive injury is unknown. Here, paired corticospinal-motoneuronal stimulation (PCMS) was administered to increase cortico-spinal connectivity of the residual tract in humans with longstanding hand impairment due to stroke. Diffusion MRI was used to reconstruct the residual corticofugal projection from primary motor cortex. We found that fractional anisotropy of fibers within the region directly damaged by stroke accounted for 49.2 % of the variance in facilitation of motor-evoked potentials elicited by single-pulse transcranial magnetic stimulation. White matter volume within the damaged region was only weakly correlated with the observed change. Microstructure in caudal portions of the residual tract subject to secondary degeneration strongly predicted voluntary and stimulation-evoked activation of spinal motor neurons pools innervating the paretic hand but were unrelated to PCMS aftereffects. Our findings provide preliminary evidence to indicate that microstructural integrity of fibers directly damaged by stroke, and not the overall volume that remains, predicts the effect of noninvasive neuromodulation mediated downstream in the spinal cord.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00607"},"PeriodicalIF":5.6,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Prolonged exposure to leisure screen time notably accelerates biological aging: Evidence from observational studies and genetic associations. 长时间暴露在休闲屏幕前明显加速生物衰老：来自观察性研究和遗传关联的证据。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2025-05-10 DOI: 10.1016/j.neurot.2025.e00599

Jie Wen, Yuchen Wang, Xueyi Mao, Ruoyan Lei, Jinglin Zhou, Jingwei Zhang, Hongwei Liu, Quan Cheng

{"title":"Prolonged exposure to leisure screen time notably accelerates biological aging: Evidence from observational studies and genetic associations.","authors":"Jie Wen, Yuchen Wang, Xueyi Mao, Ruoyan Lei, Jinglin Zhou, Jingwei Zhang, Hongwei Liu, Quan Cheng","doi":"10.1016/j.neurot.2025.e00599","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00599","url":null,"abstract":"LST is steadily increasing and is associated with various health issues. However, its impact on aging remains unclear. A total of 7212 participants from NHANES 1999-2002 were included. LTL, ALM, and FI were selected as aging phenotypes. Observational association between LST and aging traits was analyzed using linear regression models. MR analyses based on 112 genetic variants were performed to test the causal estimates from LST on aging. TWAS and PPI analyses were conducted to investigate underlying biological mechanisms. After adjusting for physical activity, per 1 h increase in LST, participants had a shorter LTL (β = -1.39, 95 % CI: -2.47 to -0.30), a lower ALM (β = -1.09, 95 % CI: -1.39 to -0.70), and an increased FI (β = 8.22, 95 % CI: 4.29 to 12.30). Likewise, TSMR analyses indicated that genetically increased LST was significantly associated with shorter LTL (β = -2.63, 95 % CI: -4.86 to -0.35), lower ALM (β = -6.56, 95 % CI: -9.43 to -3.60), and increased FI (β = 20.16, 95 % CI: 15.73 to 24.77). The trend remained robust after tests for pleiotropy and heterogeneity, consistent with the results of MVMR. 4 hub genes and 15 co-localized genes are identified, respectively, from PPI networks and TWAS. Pathways related to immune reactions, oxidative stress, and protein metabolism were significantly enriched. This study revealed that increased LST is significantly associated with adverse aging phenotypes. Reducing LST may help alleviate the burden of aging.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00599"},"PeriodicalIF":5.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Repair mechanisms of the central nervous system: From axon sprouting to remyelination. 中枢神经系统的修复机制：从轴突发芽到髓鞘再生。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2025-05-09 DOI: 10.1016/j.neurot.2025.e00583

Lauren Gluck, Brittany Gerstein, Ulrike W Kaunzner

{"title":"Repair mechanisms of the central nervous system: From axon sprouting to remyelination.","authors":"Lauren Gluck, Brittany Gerstein, Ulrike W Kaunzner","doi":"10.1016/j.neurot.2025.e00583","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00583","url":null,"abstract":"The central nervous system (CNS), comprising the brain, spinal cord, and optic nerve, has limited regenerative capacity, posing significant challenges in treating neurological disorders. Recent advances in neuroscience and neurotherapeutics have introduced promising strategies to stimulate CNS repair, particularly in the context of neurodegenerative diseases such as multiple sclerosis. This review explores the complex interplay between inflammation, demyelination, and remyelination possibilities. Glial cells, including oligodendrocyte precursors, oligodendrocytes, astrocytes and microglia play dual roles in injury response, with reactive gliosis promoting repair but also potentially inhibiting recovery through glial scar formation. There is also an emphasis on axonal regeneration, axonal sprouting and stem cell therapies. We highlight the role of neuroplasticity in recovery post-injury and the limited regenerative potential of axons in the CNS due to inhibitory factors such as myelin-associated inhibitors. Moreover, neurotrophic factors support neuronal survival and axonal growth, while stem cell-based approaches offer promise for replacing lost neurons and glial cells. However, challenges such as stem cell survival, integration, and risk of tumor formation remain. Furthermore, we examine the role of neurogenesis in CNS repair and the remodeling of the extracellular matrix, which can facilitate regeneration. Through these diverse mechanisms, ongoing research aims to overcome the intrinsic and extrinsic barriers to CNS repair and advance therapeutic strategies for neurological diseases.","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00583"},"PeriodicalIF":5.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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