Molecular Neurobiology最新文献_第4页

Enterococcus faecalis Exerts Neuroprotective Effects via the Vagus Nerve in a Mouse Model of Parkinson's Disease. 粪肠球菌通过迷走神经在帕金森病小鼠模型中发挥神经保护作用。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-15 DOI: 10.1007/s12035-025-04741-8

Xian Shao, Tao Wu, Mengyun Li, Matao Zheng, Hui Lin, Xuchen Qi

{"title":"Enterococcus faecalis Exerts Neuroprotective Effects via the Vagus Nerve in a Mouse Model of Parkinson's Disease.","authors":"Xian Shao, Tao Wu, Mengyun Li, Matao Zheng, Hui Lin, Xuchen Qi","doi":"10.1007/s12035-025-04741-8","DOIUrl":"10.1007/s12035-025-04741-8","url":null,"abstract":"Parkinson's disease (PD) is a common neurodegenerative disease worldwide. Current treatment methods for PD are unable to halt disease progression. The gut microbiota contributes to the neurodevelopment of PD; however, the gut-brain connections and underlying neural bases that regulate this complex behavior are not yet clear. Enterococcus faecalis (EF) is a common commensal bacterium of the gut and a common pathogen associated with hospital-acquired infections. Here, we demonstrated the significant therapeutic effects of a non-pathogenic strain of EF (EF ATCC19433) on PD. In this study, we established a mouse model of PD by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We found that EF treatment alleviated behavioral impairment, dopaminergic neuronal loss, blood-brain barrier damage, and neuroinflammation induced by MPTP in the mice. Additionally, 16S rRNA sequencing revealed that dysbiosis of PD-related microbial communities induced by MPTP was reversed by EF treatment. Moreover, EF treatment relieved gastrointestinal dysfunction in the mice. The therapeutic efficacy of EF in MPTP-induced PD mice is markedly diminished when the activity of EF is lost. Further mechanistic studies indicated that the neuroprotective effects of EF in PD were associated with the vagus nerve pathway. Following the surgical severance of the vagus nerve through subdiaphragmatic vagotomy, the protective effects of EF on PD were markedly diminished. Our study suggests that EF can alleviate neurofunctional impairments and gastrointestinal disorders associated with PD, indicating that gut-derived microbes influence brain function through the vagus nerve pathway.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7875-7891"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425420","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

PARP-16 regulates the PERK and IRE-1α Mediated Unfolded Protein Response in Japanese Encephalitis Virus-Infected Neural Stem/Progenitor Cells. PARP-16调控日本脑炎病毒感染的神经干/祖细胞PERK和IRE-1α介导的未折叠蛋白反应。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-20 DOI: 10.1007/s12035-025-04748-1

Shivangi Sharma, Anirudh Satheesan, Atreye Majumdar, Sriparna Mukherjee, Anirban Basu

{"title":"PARP-16 regulates the PERK and IRE-1α Mediated Unfolded Protein Response in Japanese Encephalitis Virus-Infected Neural Stem/Progenitor Cells.","authors":"Shivangi Sharma, Anirudh Satheesan, Atreye Majumdar, Sriparna Mukherjee, Anirban Basu","doi":"10.1007/s12035-025-04748-1","DOIUrl":"10.1007/s12035-025-04748-1","url":null,"abstract":"The viral infection and subsequent accumulation of viral proteins in the infected cells leads to endoplasmic reticulum (ER) stress. Japanese encephalitis virus (JEV) infection in the Central Nervous System (CNS) has been shown to induce unfolded protein response (UPR). The ER stress is resolved by the UPR which comprises certain signals that are transduced from the ER either to both the cytoplasm or nucleus, resulting in the adaptation for survival or may even lead to apoptosis. Here, we demonstrate that Poly ADP-ribose polymerase-16 (PARP-16) expression is regulating the ER stress response following JEV infection of Neural Stem/Progenitor cells (NSPCs) in the BALB/c mouse model. Activation of the key sensors of UPR, namely, protein kinase R (PKR)-like ER kinase (PERK) and Inositol-requiring enzyme-1α (IRE-1α) by PARP-16 upon JEV infection, led to the activation of their downstream signalling cascade. The siRNA-mediated in vitro downregulation of PARP-16 in NSPCs alleviated the overall UPR, as the abundance of UPR markers and their downstream modulators of signalling cascade was found to be downregulated. These results highlight an important role of PARP-16 during JEV infection of NSPCs.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8084-8096"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468725","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

CD28 Superfamily Costimulatory Molecules in Chronic Pain: Focus on Immunomodulation. 慢性疼痛中的CD28超家族共刺激分子：关注免疫调节。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-16 DOI: 10.1007/s12035-025-04746-3

Qinglu Shi, Yujia Luo, Qiaomin Xiang, Xianhui Kang, Zhiying Feng

引用次数: 0

Mitochondrial Treatment Improves Cognitive Impairment Induced by Lipopolysaccharide in Mice. 线粒体治疗可改善脂多糖对小鼠认知能力的损害

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2024-07-22 DOI: 10.1007/s12035-024-04368-1

Qiu-Qing Yan, Tian-Long Liu, Ling-Ling Liu, Yan-Su Wei, Yuan-Dan Zhao, Chao Yu, Zhen-Guo Zhong, Jin-Lan Huang, Deng-Pan Wu

{"title":"Mitochondrial Treatment Improves Cognitive Impairment Induced by Lipopolysaccharide in Mice.","authors":"Qiu-Qing Yan, Tian-Long Liu, Ling-Ling Liu, Yan-Su Wei, Yuan-Dan Zhao, Chao Yu, Zhen-Guo Zhong, Jin-Lan Huang, Deng-Pan Wu","doi":"10.1007/s12035-024-04368-1","DOIUrl":"10.1007/s12035-024-04368-1","url":null,"abstract":"Neuroinflammation has been proven to drive cognitive impairment associated with neurodegenerative diseases. It has been demonstrated that mitochondrial dysfunction is associated with cognitive impairment caused by neuroinflammation. We hypothesized that the transfer of exogenous mitochondria may be beneficial to the therapy of cognitive impairment induced by neuroinflammation. In the study, the effect of exogenous mitochondria on cognitive impairment induced by neuroinflammation was investigated. The results showed that mitochondrial treatment ameliorated the cognitive performance of lipopolysaccharide (LPS)-treated mice. Additionally, mitochondrial therapy attenuated neuronal injury and down-regulated the expression of proinflammatory cytokines, including TNF-α and pro- and cleaved IL-1β, and the expression of Iba-1 and GFAP in the hippocampus and cortex of LPS-treated mice. Additionally, mitochondrial treatment increased mitochondrial ΔΨm, ATP level, and SOD activity and attenuated MDA level and ROS production in the brains of LPS-treated mice. The study reports the beneficial effect of mitochondrial treatment against cognitive impairment of LPS-treated mice, thereby providing a potential strategy for the treatment of cognitive impairment caused by neuroinflammation.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6703-6714"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734572","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

Versatility of Caenorhabditis elegans as a Model Organism for Evaluating Foodborne Neurotoxins and Food Bioactive Compounds in Nutritional Neuroscience. 草履虫作为营养神经科学中评估食源性神经毒素和食品生物活性化合物的模式生物的多功能性。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-01-25 DOI: 10.1007/s12035-025-04705-y

Isaac A Adedara, Grazielle C C Weis, Camila S Monteiro, Felix A A Soares, Joao B T Rocha, Maria R C Schetinger, Tatiana Emanuelli, Michael Aschner

{"title":"Versatility of Caenorhabditis elegans as a Model Organism for Evaluating Foodborne Neurotoxins and Food Bioactive Compounds in Nutritional Neuroscience.","authors":"Isaac A Adedara, Grazielle C C Weis, Camila S Monteiro, Felix A A Soares, Joao B T Rocha, Maria R C Schetinger, Tatiana Emanuelli, Michael Aschner","doi":"10.1007/s12035-025-04705-y","DOIUrl":"10.1007/s12035-025-04705-y","url":null,"abstract":"Epidemiological evidence has shown that the regular ingestion of vegetables and fruits is associated with reduced risk of developing chronic diseases. The introduction of the 3Rs (replacement, reduction, and refinement) principle into animal experiments has led to the use of valid, cost-effective, and efficient alternative and complementary invertebrate animal models which are simpler and lower in the phylogenetic hierarchy. Caenorhabditis elegans (C. elegans), a nematode with a much simpler anatomy and physiology compared to mammals, share similarities with humans at the cellular and molecular levels, thus making it a valid model organism in neurotoxicology. This review explores the versatility of C. elegans in elucidating the neuroprotective mechanisms elicited by food bioactive compounds against neurotoxic effects of food- and environmental-related contaminants. Several signaling pathways linked to the molecular basis of neuroprotection exerted by bioactive compounds in chemically induced or transgenic C. elegans models of neurodegenerative diseases are also discussed. Specifically, the modulatory effects of bioactive compounds on the DAF-16/FoxO and SKN-1/Nrf2 signaling pathways, stress resistance- and autophagy-related genes, and antioxidant defense enzyme activities were highlighted. Altogether, C. elegans represent a valuable model in nutritional neuroscience for the identification of promising neuroprotective agents and neurotherapeutic targets which could help in overcoming the limitations of current therapeutic agents for neurotoxicity and neurodegenerative diseases.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7205-7229"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040257","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

Toll-Like Receptor 4-Mediated Neuroinflammation: Updates on Pathological Roles and Therapeutic Strategies in Chronic Cerebral Hypoperfusion. toll样受体4介导的神经炎症：慢性脑灌注不足的病理作用和治疗策略的最新进展。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-01-28 DOI: 10.1007/s12035-025-04718-7

Nuttapong Yawoot, Jiraporn Tocharus, Chainarong Tocharus

{"title":"Toll-Like Receptor 4-Mediated Neuroinflammation: Updates on Pathological Roles and Therapeutic Strategies in Chronic Cerebral Hypoperfusion.","authors":"Nuttapong Yawoot, Jiraporn Tocharus, Chainarong Tocharus","doi":"10.1007/s12035-025-04718-7","DOIUrl":"10.1007/s12035-025-04718-7","url":null,"abstract":"Neuroinflammation has been acknowledged as being one of the main pathologies that occur following chronic cerebral hypoperfusion (CCH). Since it significantly contributes to neuronal cell damage and thereby leads to cognitive impairment, the signals related to inflammation in hypoperfusion injury have been extensively investigated over the past few years. Toll-like receptor 4 (TLR4) is the key receptor responsible for immune and inflammatory reactions. It has been reported that TLR4 is involved in the pathology of several diseases and has emerged as a therapeutic target for developing a variety of anti-inflammatory compounds. This study explored the pathological roles of TLR4 that potentially cause the promotion of neuroinflammation in CCH damage. The evidence pertinent to the activation of TLR4 and its downstream inflammatory cascades following CCH are also summarized. This study also demonstrated the therapeutic potential of TLR4 inhibition, whether through drugs, substances, or other treatment strategies, in models of CCH-induced neurological dysfunction. The limitations of the accumulated evidence are addressed and discussed in this study. A deeper understanding of the roles of TLR4 in neuroinflammation following CCH damage may help inform the machinery behind pathological processes for advancing further neuroscientific research and developing therapeutic strategies for vascular dementia.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7242-7267"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059599","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

Involvement of CRMP2 Phosphorylation in Amyloid Beta-induced Tau Phosphorylation of Hippocampal Neurons in Alzheimer's Disease Mouse Model. CRMP2磷酸化参与淀粉样蛋白β诱导的阿尔茨海默病小鼠模型海马神经元Tau磷酸化

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-01 DOI: 10.1007/s12035-025-04721-y

Daisuke Noguchi, Naoto Watamura, Miyu Nikkuni, Takaomi C Saido, Yoshio Goshima, Toshio Ohshima

{"title":"Involvement of CRMP2 Phosphorylation in Amyloid Beta-induced Tau Phosphorylation of Hippocampal Neurons in Alzheimer's Disease Mouse Model.","authors":"Daisuke Noguchi, Naoto Watamura, Miyu Nikkuni, Takaomi C Saido, Yoshio Goshima, Toshio Ohshima","doi":"10.1007/s12035-025-04721-y","DOIUrl":"10.1007/s12035-025-04721-y","url":null,"abstract":"Alzheimer's disease (AD) is the most common form of dementia, characterized by amyloid-β (Aβ) deposition and the formation of neurofibrillary tangles composed of hyperphosphorylated tau. Collapsin response mediator protein 2 (CRMP2), a microtubule (MT)-binding protein, regulates MT dynamics and is phosphorylated at Ser522 by cyclin-dependent kinase 5. Previous studies have shown increased CRMP2 phosphorylation at Ser522 (CRMP2-pSer522) in early AD stages and AD mouse models, where it colocalizes with phosphorylated tau. However, the role of CRMP-pSer522 in AD pathology remains unclear. In this study, we generated double transgenic mice by crossing tau Tg (PS19) mice and CRMP2 S522A knock-in (CRMP2KI) mice, in which S522 of CRMP2 was replaced with alanine to create a phospho-defective model. No significant change in tau phosphorylation was observed in the hippocampus of tau Tg; CRMP2KI mice compared to tau Tg littermates. However, when Aβ25-35 oligomers were injected into the hippocampus, tau phosphorylation was significantly reduced in Aβ-injected tau Tg; CRMP2KI mice compared to Aβ-injected tau Tg controls. These findings suggest that CRMP2 phosphorylation at Ser522 promotes Aβ-induced tau phosphorylation in this mouse model of AD.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7413-7420"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075272","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 Metabolic Profile of Plasma During Epileptogenesis in a Rat Model of Lithium-Pilocarpine-Induced Temporal Lobe Epilepsy. 锂-匹洛卡品诱导颞叶癫痫大鼠模型癫痫发生过程中血浆代谢谱的研究。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-04 DOI: 10.1007/s12035-025-04719-6

Fatma Merve Antmen, Emir Matpan, Ekin Dongel Dayanc, Eylem Ozge Savas, Yunus Eken, Dilan Acar, Alara Ak, Begum Ozefe, Damla Sakar, Ufuk Canozer, Sehla Nurefsan Sancak, Ozkan Ozdemir, Osman Ugur Sezerman, Ahmet Tarık Baykal, Mustafa Serteser, Guldal Suyen

{"title":"The Metabolic Profile of Plasma During Epileptogenesis in a Rat Model of Lithium-Pilocarpine-Induced Temporal Lobe Epilepsy.","authors":"Fatma Merve Antmen, Emir Matpan, Ekin Dongel Dayanc, Eylem Ozge Savas, Yunus Eken, Dilan Acar, Alara Ak, Begum Ozefe, Damla Sakar, Ufuk Canozer, Sehla Nurefsan Sancak, Ozkan Ozdemir, Osman Ugur Sezerman, Ahmet Tarık Baykal, Mustafa Serteser, Guldal Suyen","doi":"10.1007/s12035-025-04719-6","DOIUrl":"10.1007/s12035-025-04719-6","url":null,"abstract":"Temporal lobe epilepsy (TLE) arises mostly because of an initial injury. Certain stimuli can make a normal brain prone to repeated, spontaneous seizures via a process called epileptogenesis. This study examined the plasma metabolomics profile in rats with the induced TLE to identify feasible biomarkers that can distinguish progression of epileptogenesis in three different time points and reveal the underlying mechanisms of epileptogenesis. Status epilepticus (SE) was induced by repetitive intraperitoneal injections of low-dose lithium chloride-pilocarpine hydrocholoride. Blood samples were collected 48 h, 1 week, and 6 weeks after SE, respectively. Plasma metabolites were analyzed by nuclear magnetic resonance (NMR) spectrometry. Statistical analysis was performed using MetaboAnalyst 6.0. An orthogonal partial least squares discriminant analysis (OPLS-DA) model was employed to represent variations between the TLE model groups and respective controls. Volcano plot analysis was used to identify key features, applying a fold-change criterion of 1.5 and a t-test threshold of 0.05. 48 h after SE, dimethyl sulfone (DMSO2) and creatinine levels were decreased, whereas glycine and creatine levels were increased. The only metabolite that changed 1 week after SE was pyruvic acid, which was increased compared to its control level. Lactic acid, pyruvic acid, and succinic acid levels were increased 6 weeks after SE. The identified metabolites were especially related to the tricarboxylic acid cycle and glycine, serine, and threonine metabolism. The results illustrate that distinct plasma metabolites can function as phase-specific biomarkers in TLE and reveal new insights into the mechanisms underlying SE.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7469-7483"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189836","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

Lasting Impact: Exploring the Brain Mechanisms that Link Traumatic Brain Injury to Parkinson's Disease. 持久影响：探索将创伤性脑损伤与帕金森病联系起来的脑机制。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-02-01 DOI: 10.1007/s12035-025-04706-x

Samantha Edwards, Frances Corrigan, Lyndsey Collins-Praino

{"title":"Lasting Impact: Exploring the Brain Mechanisms that Link Traumatic Brain Injury to Parkinson's Disease.","authors":"Samantha Edwards, Frances Corrigan, Lyndsey Collins-Praino","doi":"10.1007/s12035-025-04706-x","DOIUrl":"10.1007/s12035-025-04706-x","url":null,"abstract":"Development of Parkinson's Disease (PD) is linked with a history of traumatic brain injury (TBI), although the mechanisms driving this remain unclear. Of note, many key parallels have been identified between the pathologies of PD and TBI; in particular, PD is characterised by loss of dopaminergic neurons from the substantia nigra (SN), accompanied by broader changes to dopaminergic signalling, disruption of the Locus Coeruleus (LC) and noradrenergic system, and accumulation of aggregated α-synuclein in Lewy Bodies, which spreads in a stereotypical pattern throughout the brain. Widespread disruptions to the dopaminergic and noradrenergic systems, including progressive neuronal loss from the SN and LC, have been observed acutely following injury, some of which have also been identified chronically in TBI patients and preclinical models. Furthermore, changes to α-synuclein expression are also seen both acutely and chronically following injury throughout the brain, although detailed characterisation of these changes and spread of pathology is limited. In this review, we detail the current literature regarding dopaminergic and noradrenergic disruption and α-synuclein pathology following injury, with particular focus on how these changes may predispose individuals to prolonged pathology and progressive neurodegeneration, particularly the development of PD. While it is increasingly clear that TBI is a key risk factor for the development of PD, significant gaps remain in current understanding of neurodegenerative pathology following TBI, particularly chronic manifestations of injury.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7421-7444"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075275","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

Prospective Investigation Unravels Plasma Proteomic Links to Dementia. 前瞻性研究揭示了血浆蛋白质组学与痴呆的联系。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-06-01 Epub Date: 2025-01-30 DOI: 10.1007/s12035-025-04716-9

Jincheng Li, Jialin Li, Shuaizhou Chen, Zhenqiu Liu, Jiacheng Dai, Yingzhe Wang, Mei Cui, Chen Suo, Kelin Xu, Li Jin, Xingdong Chen, Yanfeng Jiang

{"title":"Prospective Investigation Unravels Plasma Proteomic Links to Dementia.","authors":"Jincheng Li, Jialin Li, Shuaizhou Chen, Zhenqiu Liu, Jiacheng Dai, Yingzhe Wang, Mei Cui, Chen Suo, Kelin Xu, Li Jin, Xingdong Chen, Yanfeng Jiang","doi":"10.1007/s12035-025-04716-9","DOIUrl":"10.1007/s12035-025-04716-9","url":null,"abstract":"Investigating plasma proteomic signatures of dementia offers insights into its pathology, aids biomarker discovery, supports disease monitoring, and informs drug development. Here, we analyzed data from 48,367 UK Biobank participants with proteomic profiling. Using Cox and generalized linear models, we examined the longitudinal associations between proteomic signatures and dementia-related phenotypes. Mendelian randomization analysis was employed to identify causal associations, and machine learning algorithms were applied to develop protein-based models for dementia prediction. We identified 74 proteins significantly associated with the risk of various types of dementia and cognitive functions after Bonferroni correction. Among these, strong associations were observed for growth/differentiation factor 15 (GDF15), glial fibrillary acidic protein (GFAP), and neurofilament light polypeptide (NEFL), across all types of dementia. Additionally, 15 proteins demonstrated significant associations with neuroimaging-defined dementia endophenotypes. Two-sample Mendelian randomization analyses further substantiated causal relationships between dementia-associated proteins and Alzheimer's disease, particularly involving GDF15, proto-oncogene tyrosine-protein kinase receptor Ret (RET), and GFAP. Moreover, we identified three protein modules associated with dementia, primarily linked to immune system processes, angiogenesis, and energy metabolism, providing insights into potential biological pathways underlying the disease. Furthermore, we proposed a ten-protein panel capable of forecasting dementia over a median follow-up period of 8.6 years, achieving an area under the curve (AUC) of 0.857 (95% confidence interval (CI), 0.837-0.876). Our results revealed dementia-associated plasma proteomic signatures, and their causal relationships, notably GDF15-RET signaling with Alzheimer's disease, and proposed a promising protein panel for high-risk dementia screening.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7345-7360"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066746","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