Molecular Neurobiology最新文献_第3页

The Effect of Picein on Inhibitory Avoidance Memory and Activity of Antioxidant Enzymes in Hippocampus of Male Rats with Scopolamine-Induced Injury. 青松素对东莨菪碱损伤大鼠海马抗氧化酶活性及抑制性回避记忆的影响。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-13 DOI: 10.1007/s12035-025-04740-9

Leila Elyasi, Jessica M Rosenholm, Mehrdad Jahanshahi, Fatemeh Jesmi

{"title":"The Effect of Picein on Inhibitory Avoidance Memory and Activity of Antioxidant Enzymes in Hippocampus of Male Rats with Scopolamine-Induced Injury.","authors":"Leila Elyasi, Jessica M Rosenholm, Mehrdad Jahanshahi, Fatemeh Jesmi","doi":"10.1007/s12035-025-04740-9","DOIUrl":"10.1007/s12035-025-04740-9","url":null,"abstract":"Alzheimer disease (AD) is a common neurologic disorder, impairing memory and spatial perception. Consistent with the extensive search for its treatment, we investigated the effect of Picein on inhibitory avoidance memory, lipid peroxidation, and the activity of hippocampal antioxidant enzymes in rats. Forty adult male Wistar rats were randomized into control group (no intervention), model group (intraperitoneal injection of 3-mg/kg scopolamine), and three interventional groups (1.5-, 2.5-, and 5-mg/kg intraventricular Picein, once a day for 7 days, 24 h after scopolamine injection). After behavioral test, the rats' hippocampus was isolated for measuring oxidative stress markers, including enzymes superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC). One-way ANOVA was used for comparing numeric variables among the groups using SPSS v.21. The results showed scopolamine decreased SOD, GPX, and CAT enzymes, and TAC level, and increased MDA level, compared with the control group (P < 0.001) that confirmed the scopolamine-induced AD model. The two doses of 2.5- and 5-mg/kg Picein increased latency for entering the dark room, compared to the scopolamine group (P < 0.05), making them similar to the control group. The number of entries into the dark room in the 2.5-mg/kg Picein reduced and approached the control group (P < 0.05). The 2.5-mg/kg Picein decreased MDA and increased SOD, GPX, and TAC, more than 5 mg/kg Picein, both different than scopolamine; only 2.5-mg/kg Picein had different CAT, compared to scopolamine group (P < 0.05). In conclusion, by lowering oxidative stress in the hippocampus, Picein was able to prevent the scopolamine-induced impaired learning and avoidance memory in rats.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7835-7845"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408468","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

IGF1R/ARRB1 Mediated Regulation of ERK and cAMP Pathways in Response to Aβ Unfolds Novel Therapeutic Avenue in Alzheimer's Disease. IGF1R/ARRB1介导的ERK和cAMP通路对Aβ的反应揭示了阿尔茨海默病的新治疗途径

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-19 DOI: 10.1007/s12035-025-04735-6

Priyanka Sengupta, Debashis Mukhopadhyay

{"title":"IGF1R/ARRB1 Mediated Regulation of ERK and cAMP Pathways in Response to Aβ Unfolds Novel Therapeutic Avenue in Alzheimer's Disease.","authors":"Priyanka Sengupta, Debashis Mukhopadhyay","doi":"10.1007/s12035-025-04735-6","DOIUrl":"10.1007/s12035-025-04735-6","url":null,"abstract":"IGF1R/INSR signaling is crucial for understanding Alzheimer's disease (AD) and may aid in the development of potent therapeutic strategies. This study investigated the expression and activity of these receptors and their potential to form functional hybrids in response to amyloid beta (Aβ). IGF1R, INSR, and ARRB1 were found to be upregulated in AD. The propensity for functional hybrid formation was also greater in the presence of Aβ. The association of IGF1R with ARRB1 reached a maximum at 60 min of Aβ treatment, which coincided with increased pERK activity at approximately the same time, indicating the importance of this association in pERK regulation. Knocking down IGF1R, INSR, and ARRB1 independently reduced cAMP, whereas overexpressing IGF1R significantly increased cAMP. Knocking down ARRB1 in IGF1R-overexpressing cells led to a reduction in cAMP, indicating that the interaction of ARRB1 and IGF1R possibly contributes to cAMP dysregulation. Since cAMP plays a crucial role in cognition and memory, alterations in cAMP after receptor hybridization could be significant in AD. Additionally, we noted hyperactivation of MAPK, which is associated with aberrant cellular activity, transcriptional control, and stress pathways. This finding highlights the importance of IGF1R and INSR dysregulation, which plays a major role in addition to conventional RTK signaling through multiple pathways. Here, we focused on the ARRB1 and IGF1R interaction and showed that picropodophyllin (PPP), an IGF1R-specific inhibitor, blocks this interaction and alters the ERK and cAMP status under disease conditions. Cell viability studies further revealed that the PPP substantially improved cell viability in the presence of Aβ. This highlights the role of the PPP in regulating these cascades and opens the arena for further therapeutic development for AD.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8065-8083"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449706","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

Selenium Nanoparticles as Neuroprotective Agents: Insights into Molecular Mechanisms for Parkinson's Disease Treatment. 作为神经保护剂的硒纳米粒子：帕金森病治疗的分子机制透视。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2024-06-05 DOI: 10.1007/s12035-024-04253-x

Suganiya Umapathy, Ieshita Pan, Praveen Kumar Issac, Meenakshi Sundaram Kishore Kumar, Jayant Giri, Ajay Guru, Jesu Arockiaraj

{"title":"Selenium Nanoparticles as Neuroprotective Agents: Insights into Molecular Mechanisms for Parkinson's Disease Treatment.","authors":"Suganiya Umapathy, Ieshita Pan, Praveen Kumar Issac, Meenakshi Sundaram Kishore Kumar, Jayant Giri, Ajay Guru, Jesu Arockiaraj","doi":"10.1007/s12035-024-04253-x","DOIUrl":"10.1007/s12035-024-04253-x","url":null,"abstract":"Oxidative stress and the accumulation of misfolded proteins in the brain are the main causes of Parkinson's disease (PD). Several nanoparticles have been used as therapeutics for PD. Despite their therapeutic potential, these nanoparticles induce multiple stresses upon entry. Selenium (Se), an essential nutrient in the human body, helps in DNA formation, stress control, and cell protection from damage and infections. It can also regulate thyroid hormone metabolism, reduce brain damage, boost immunity, and promote reproductive health. Selenium nanoparticles (Se-NPs), a bioactive substance, have been employed as treatments in several disciplines, particularly as antioxidants. Se-NP, whether functionalized or not, can protect mitochondria by enhancing levels of reactive oxygen species (ROS) scavenging enzymes in the brain. They can also promote dopamine synthesis. By inhibiting the aggregation of tau, α-synuclein, and/or Aβ, they can reduce the cellular toxicities. The ability of the blood-brain barrier to absorb Se-NPs which maintain a healthy microenvironment is essential for brain homeostasis. This review focuses on stress-induced neurodegeneration and its critical control using Se-NP. Due to its ability to inhibit cellular stress and the pathophysiologies of PD, Se-NP is a promising neuroprotector with its anti-inflammatory, non-toxic, and antimicrobial properties.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6655-6682"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247799","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

P2Y6R Inhibition Induces Microglial M2 Polarization by Promoting PINK1/Parkin-Dependent Mitophagy After Spinal Cord Injury. 脊髓损伤后，P2Y6R 抑制通过促进 PINK1/Parkin 依赖性丝裂吞噬诱导小胶质细胞 M2 极化

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2024-11-28 DOI: 10.1007/s12035-024-04631-5

Jiezhao Lin, Yuanfang Sun, Haoran Huang, Cheng Yu, Wenhao Kuang, Yihan Wang, Lixin Zhu

{"title":"P2Y6R Inhibition Induces Microglial M2 Polarization by Promoting PINK1/Parkin-Dependent Mitophagy After Spinal Cord Injury.","authors":"Jiezhao Lin, Yuanfang Sun, Haoran Huang, Cheng Yu, Wenhao Kuang, Yihan Wang, Lixin Zhu","doi":"10.1007/s12035-024-04631-5","DOIUrl":"10.1007/s12035-024-04631-5","url":null,"abstract":"Secondary injury presents a significant hurdle to neural regeneration following spinal cord injury (SCI), primarily driven by inflammation in which microglial cells play a crucial role. Despite the growing interest in mitophagy, studies on its occurrence post-spinal cord injury, particularly within microglial cells, are scarce. While P2Y6R has been implicated in inflammation regulation in various neurological conditions, its specific role in SCI remains uncertain. Our study revealed an upregulation of P2Y6R expression following SCI notably in microglial cells. Treatment with the P2Y6R-specific inhibitor, MRS2578, in mice facilitated M2 polarization of microglial cells and alleviated secondary damage, ultimately enhancing neural regeneration and functional recovery. In an in vitro BV2 inflammation model, our findings indicate that P2Y6R inhibition induced M2 polarization of BV2 cells and reduced neuroinflammation through PINK/Parkin-dependent mitophagy activation. In summary, our results underscore the potential of P2Y6R inhibition in promoting mitophagy-induced M2 polarization of microglial cells, thereby ameliorating secondary injury following spinal cord injury.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7054-7074"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739907","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

Abdominal LIPUS Stimulation Prevents Cognitive Decline in Hind Limb Unloaded Mice by Regulating Gut Microbiota. 腹部脂肪刺激通过调节肠道微生物群防止后肢卸车小鼠认知能力下降。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-01-29 DOI: 10.1007/s12035-025-04709-8

Yumei Zheng, Yanan Yu, Mengyao Chen, Huiyuan Zhang, Wanzhao Wang, Xiushan Fan, Lijun Sun, Liang Tang, Dean Ta

{"title":"Abdominal LIPUS Stimulation Prevents Cognitive Decline in Hind Limb Unloaded Mice by Regulating Gut Microbiota.","authors":"Yumei Zheng, Yanan Yu, Mengyao Chen, Huiyuan Zhang, Wanzhao Wang, Xiushan Fan, Lijun Sun, Liang Tang, Dean Ta","doi":"10.1007/s12035-025-04709-8","DOIUrl":"10.1007/s12035-025-04709-8","url":null,"abstract":"Weightlessness usually causes disruption of the gut microbiota and impairs cognitive function. There is a close connection between gut microbiota and neurological diseases. Low-intensity pulsed ultrasound (LIPUS) has a beneficial effect on reducing intestinal inflammation. So we wondered if abdominal LIPUS stimulation can have a positive impact on weightlessness induced cognitive decline by reducing intestinal dysfunction. The findings revealed that the hind limb unloaded mice exhibited evident disruption in intestinal structure and gut microbial homeostasis, along with impairment in their learning and memory capabilities. However, 4-week abdominal LIPUS treatment improved intestinal function in hind limb unloaded mice, characterized by upregulation of tight junction proteins ZO-1 and Occludin expression in the colon, increased diversity and abundance of intestinal microbiota, decreased serum lipopolysaccharide (LPS), and increased short chain fatty acids in colon contents. The hind limb unloaded mice treated with LIPUS exhibited heightened activity levels, improved exploratory tendencies, and significantly enhanced learning and memory faculties, and elevated expression of neuroadaptation-related proteins such as PSD95, GAP43, P-CREB, BDNF, and its receptor TRKB in the hippocampus. Furthermore, the hind limb unloaded mice receiving fecal transplants from the mice whose abdomens were irradiated with LIPUS displayed enhanced cognitive abilities and improved intestinal structure, akin to the outcomes observed in hind limb unloaded mice who received LIPUS abdominal treatment directly. The above results indicate that LIPUS enhances intestinal structure and microbiota, which helps alleviate cognitive impairment caused by weightlessness. LIPUS could be a potential strategy to simultaneously improve gut dysfunction and cognitive decline in astronauts or bedridden patients.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7313-7329"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059584","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

The Role of ΔFosB in the Pathogenesis of Levodopa-Induced Dyskinesia: Mechanisms and Therapeutic Strategies. ΔFosB在左旋多巴诱导的运动障碍发病机制中的作用：机制和治疗策略。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-01-31 DOI: 10.1007/s12035-025-04720-z

Mohammad Yasin Zamanian, Zahra Kamran, Marziye Ranjbar Tavakoli, Enwa Felix Oghenemaro, Mohammad Abohassan, Aziz Kubaev, Deepak Nathiya, Parjinder Kaur, Ahmed Hussein Zwamel, Resan Shakir Abdulamer

{"title":"The Role of ΔFosB in the Pathogenesis of Levodopa-Induced Dyskinesia: Mechanisms and Therapeutic Strategies.","authors":"Mohammad Yasin Zamanian, Zahra Kamran, Marziye Ranjbar Tavakoli, Enwa Felix Oghenemaro, Mohammad Abohassan, Aziz Kubaev, Deepak Nathiya, Parjinder Kaur, Ahmed Hussein Zwamel, Resan Shakir Abdulamer","doi":"10.1007/s12035-025-04720-z","DOIUrl":"10.1007/s12035-025-04720-z","url":null,"abstract":"Levodopa-induced dyskinesia (LID) represents a significant complication associated with the long-term administration of levodopa (L-DOPA) for the treatment of Parkinson's disease (PD). This review examines the critical role of ΔFosB, a transcription factor, in the pathogenesis of LID and explores potential therapeutic interventions. ΔFosB accumulates within the striatum in response to chronic dopaminergic stimulation, thereby driving maladaptive changes that culminate in dyskinesia. Its persistent expression modifies gene transcription, influencing neuronal plasticity and contributing to the sustained presence of dyskinetic movements. This study explains how ΔFosB functions at the molecular level, focusing on its connections with dopamine D1 receptors, the cAMP/PKA signaling pathway, and its regulatory effects on downstream targets such as DARPP-32 and GluA1 AMPA receptor subunits. Additionally, it examines how neuronal nitric oxide synthase (nNOS) affects ΔFosB levels and the development of LID. This review also considers the interactions between ΔFosB and other signaling pathways, such as ERK and mTOR, in the context of LID and striatal plasticity. Emerging therapeutic strategies targeting ΔFosB and its associated pathways include pharmacological interventions like ranitidine, 5-hydroxytryptophan, and carnosic acid. Furthermore, this study addresses the role of JunD, another component of the AP-1 transcription factor complex, in the pathogenesis of LID. Understanding the molecular mechanisms by which ΔFosB contributes to LID offers promising avenues for developing novel treatments that could mitigate dyskinesia and improve the quality of life for PD patients undergoing long-term L-DOPA therapy.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7393-7412"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075277","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

Grape Seed Extract Pretreatment Prevents Mitochondrial Dysfunction and NLRP3 Inflammasome-Induced Inflammatory Response in Glial Cells Exposed to Paroxetine and Quinolinic Acid. 葡萄籽提取物预处理可预防帕罗西汀和喹啉酸暴露的胶质细胞线粒体功能障碍和NLRP3炎症小体诱导的炎症反应。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-05 DOI: 10.1007/s12035-025-04730-x

Marina Rigotti, Laura Ferrazzi Finger, Fernando Joel Scariot, Alencar Kolinski Machado, Scheila de Avila E Silva, Mirian Salvador, Catia Santos Branco

{"title":"Grape Seed Extract Pretreatment Prevents Mitochondrial Dysfunction and NLRP3 Inflammasome-Induced Inflammatory Response in Glial Cells Exposed to Paroxetine and Quinolinic Acid.","authors":"Marina Rigotti, Laura Ferrazzi Finger, Fernando Joel Scariot, Alencar Kolinski Machado, Scheila de Avila E Silva, Mirian Salvador, Catia Santos Branco","doi":"10.1007/s12035-025-04730-x","DOIUrl":"10.1007/s12035-025-04730-x","url":null,"abstract":"Depression is a neuropsychiatric disorder that affects thousands of people around the world. Drug therapy is the main approach for treating this disease, but its use can cause side effects on cells. This study aimed to examine the impact of antidepressant drugs from different classes on glial (BV-2) cells in the presence or absence of grape seed extract (GSE) and quinolinic acid (QA; 1.5 mM). Cells were treated with GSE (50 μg/mL; 23 h) and then exposed to non-cytotoxic concentrations of bupropion, imipramine, paroxetine, trazodone, and venlafaxine (27-181 µM; 1 h). Principal Component Analysis (PCA) was conducted to demonstrate the best combination of drug and extract treatment. Cell viability, adenosine triphosphate (ATP) production, reactive oxygen species (ROS) and nitric oxide (NO) levels, oxidative damage to lipids (TBARS), superoxide dismutase (SOD) activity, apoptosis, and NLR family pyrin domain containing 3 (NLRP3) genetic expression were evaluated by spectrophotometry, qRT-PCR, or flow cytometry. Mitochondrial markers (CI: NADH-CoQ reductase and CIV: cytochrome c oxidase) were also studied. GSE prevented the increment in levels of ROS (13.73-72.11%), TBARS (44.1-92.77%), NO (9.5-16%), SOD (68.44-212.29%) activity, and apoptosis (10.06-17.3%) caused by antidepressant drugs. Furthermore, it prevented impairments in complexes I (22-71.5%) and IV (7.5-92.5%) activities and ATP production (8-46%). GSE also prevented the NLRP3 overexpression in BV-2 activated by QA (62%), and paroxetine (46%), defined by PCA. Our study evidences that GSE can restore redox equilibrium and prevent inflammation caused by antidepressants and/or QA in a glial microenvironment.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7110-7123"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189818","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

Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease. 泛素连接酶和去泛素化酶在阿尔茨海默病中的作用。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-11 DOI: 10.1007/s12035-025-04739-2

Fengju Jia, Lin Fu

{"title":"Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease.","authors":"Fengju Jia, Lin Fu","doi":"10.1007/s12035-025-04739-2","DOIUrl":"10.1007/s12035-025-04739-2","url":null,"abstract":"The mechanisms responsible for the accumulation of Aβ plaques and neurofibrillary tangles, composed of phosphorylated Tau protein, in Alzheimer's disease (AD) remain a mystery. Dysfunction of the ubiquitin-proteasome system (UPS) largely contributes to abnormal protein aggregation. A cascade of ubiquitinating enzymes promotes protein ubiquitination, while deubiquitylases (DUBs) regulate its reversal. Disruptions in ubiquitination and deubiquitination processes result in abnormal protein aggregation and the formation of inclusion bodies, ultimately leading to neuronal damage. Recent studies have highlighted the significant role of protein ubiquitination and deubiquitination in the pathogenesis of AD. E3 ubiquitin ligases, which facilitate protein ubiquitination, are beneficial for Aβ clearance, synaptic function, gap junction maintenance, mitophagy, and neuroinflammation. Conversely, DUBs, responsible for removing ubiquitin from substrate proteins, inhibit Aβ and Tau degradation while promoting neuroinflammation in neurons. This review provides a thorough overview of the involvement of E3 ubiquitin ligases and DUBs in AD, highlighting their diverse roles in aspects of pathophysiological processes.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7747-7761"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391232","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

Unlocking the Neuroprotective Potential of Silymarin: A Promising Ally in Safeguarding the Brain from Alzheimer's Disease and Other Neurological Disorders. 解锁水飞蓟素的神经保护潜力：保护大脑免受阿尔茨海默病和其他神经系统疾病的有希望的盟友。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-17 DOI: 10.1007/s12035-024-04654-y

Abdulmajeed G Almutary, M Yasmin Begum, Ayesha Siddiqua, Saurabh Gupta, Payal Chauhan, Karan Wadhwa, Govind Singh, Danish Iqbal, Gopalakrishnan Padmapriya, Sanjay Kumar, Navin Kedia, Rajni Verma, Ravi Kumar, Aashna Sinha, B Dheepak, Mosleh Mohammad Abomughaid, Niraj Kumar Jha

{"title":"Unlocking the Neuroprotective Potential of Silymarin: A Promising Ally in Safeguarding the Brain from Alzheimer's Disease and Other Neurological Disorders.","authors":"Abdulmajeed G Almutary, M Yasmin Begum, Ayesha Siddiqua, Saurabh Gupta, Payal Chauhan, Karan Wadhwa, Govind Singh, Danish Iqbal, Gopalakrishnan Padmapriya, Sanjay Kumar, Navin Kedia, Rajni Verma, Ravi Kumar, Aashna Sinha, B Dheepak, Mosleh Mohammad Abomughaid, Niraj Kumar Jha","doi":"10.1007/s12035-024-04654-y","DOIUrl":"10.1007/s12035-024-04654-y","url":null,"abstract":"Medicinal plants and their phytochemicals have been extensively employed worldwide for centuries to address a diverse range of ailments, boasting a history that spans several decades. These plants are considered the source of numerous medicinal compounds. For instance, silymarin is a polyphenolic flavonoid extract obtained from the milk thistle plant or Silybum marianum which has been shown to have significant neuroprotective effects and great therapeutic benefits. Neurodegenerative diseases (NDs) are a class of neurological diseases that have become more prevalent in recent years, and although treatment is available, there is no complete cure developed yet. Silymarin utilizes a range of molecular mechanisms, including modulation of MAPK, AMPK, NF-κB, mTOR, and PI3K/Akt pathways, along with various receptors, enzymes, and growth factors. These mechanisms collectively contribute to its protective effects against NDs such as Alzheimer's disease, Parkinson's disease, and depression. Despite its safety and efficacy, silymarin faces challenges related to bioavailability and aqueous solubility, hindering its development as a clinical drug. This review highlights the molecular mechanisms underlying silymarin's neuroprotective effects, suggesting its potential as a promising therapeutic strategy for NDs.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7975-7997"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433529","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

Critical Role of Rho Guanine Nucleotide Exchange Factor 4 in Brain Function. 鸟嘌呤核苷酸交换因子4在脑功能中的关键作用。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-08 DOI: 10.1007/s12035-025-04734-7

Hee Jeong Kim, Kina Lee, Kiseo Yoo, Jeong Eun Kim, Heeju Kim, Chae-Seok Lim, Young Seok Park, Hyong Kyu Kim

{"title":"Critical Role of Rho Guanine Nucleotide Exchange Factor 4 in Brain Function.","authors":"Hee Jeong Kim, Kina Lee, Kiseo Yoo, Jeong Eun Kim, Heeju Kim, Chae-Seok Lim, Young Seok Park, Hyong Kyu Kim","doi":"10.1007/s12035-025-04734-7","DOIUrl":"10.1007/s12035-025-04734-7","url":null,"abstract":"Although Rho guanine nucleotide exchange factor 4 (Arhgef4) is highly expressed in the brain, its function remains poorly understood. Our previous study showed that Arhgef4 negatively regulates excitatory postsynaptic regional activity. This study investigated the effects of Arhgef4 deletion in postnatal forebrain-specific knockout mice on brain function, synaptic proteins, and behaviors. We generated a knockout mouse with Arhgef4 deleted from the forebrain and analyzed gene expression and protein levels by RT-PCR and western blot. Synaptic function was assessed through electrophysiological recordings, and behavioral tests evaluated memory and anxiety. In these conditional knockout (cKO) mice, we observed a significant decrease in the expression of a 75-kDa brain-enriched isoform of Arhgef4 in the forebrain. In KO mice, pre- and post-synaptic protein levels were unchanged. However, in cultured hippocampal neurons from KO mice, the levels of postsynaptic density protein 95 (PSD-95) in the postsynaptic regions were significantly increased from the pre-mature stage to the fully mature stage during neuronal development. In contrast, the number of dendritic protrusions decreased during the early mature stage of the cultured neurons. Electrophysiological recordings of hippocampal neurons from KO mice showed a significant increase in miniature excitatory postsynaptic currents (mEPSC) frequency. Furthermore, Arhgef4 KO mice exhibited enhanced long-term memory and reduced anxiety-related behaviors. These findings suggest that Arhgef4 plays a role in regulating brain functions such as learning, memory, and anxiety.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7647-7663"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370881","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