NPJ Parkinson's Disease最新文献_第7页

Glutamatergic synaptic resilience to overexpressed human alpha-synuclein 谷氨酸能突触对过度表达的人α -突触核蛋白的弹性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-12 DOI: 10.1038/s41531-025-01085-x

Patrícia I. Santos, Inés Hojas García-Plaza, Ali Shaib, Jeong Seop Rhee, Abed Alrahman Chouaib, Nils Brose, Silvio O. Rizzoli, James Daniel, Tiago F. Outeiro

{"title":"Glutamatergic synaptic resilience to overexpressed human alpha-synuclein","authors":"Patrícia I. Santos, Inés Hojas García-Plaza, Ali Shaib, Jeong Seop Rhee, Abed Alrahman Chouaib, Nils Brose, Silvio O. Rizzoli, James Daniel, Tiago F. Outeiro","doi":"10.1038/s41531-025-01085-x","DOIUrl":"https://doi.org/10.1038/s41531-025-01085-x","url":null,"abstract":"Alpha synuclein (aSyn) is abundant in the brain and strongly implicated in Parkinson’s disease (PD), genetically and through its accumulation in neuronal pathognomonic inclusions. While mutations or increased expression of wild-type aSyn can cause familial PD, it remains unclear whether increased aSyn alone impairs presynaptic function. Here, we overexpressed human aSyn (haSyn) in rodent glutamatergic neurons and analysed presynaptic function. Expression levels mimicked SNCA gene triplications, as seen in certain familial forms of PD. In continental cultures, haSyn overexpression was not toxic nor did it alter the levels of presynaptic SNAP-25 or postsynaptic PSD-95. Analyses of autaptic neurons revealed no significant differences in evoked or spontaneous neurotransmission release, nor in synaptic plasticity. These results indicate that rodent glutamatergic neurons are resilient to aSyn overexpression. Our findings suggest neurotoxicity associated with aSyn overexpression is not universal, and that a deeper understanding of aSyn biology and pathobiology is necessary.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"740 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Parkinson’s disease quality of life at 12 months comparing invasive device-aided therapy with oral treatment 帕金森病12个月的生活质量比较侵入性器械辅助治疗与口服治疗

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-11 DOI: 10.1038/s41531-025-01093-x

Adolfo Ramirez-Zamora, Michael S. Okun, Pavnit Kukreja, Wei Hu

{"title":"Parkinson’s disease quality of life at 12 months comparing invasive device-aided therapy with oral treatment","authors":"Adolfo Ramirez-Zamora, Michael S. Okun, Pavnit Kukreja, Wei Hu","doi":"10.1038/s41531-025-01093-x","DOIUrl":"https://doi.org/10.1038/s41531-025-01093-x","url":null,"abstract":"Real-world impact of device-aided therapy on quality of life (QoL) in people with Parkinson’s remains unknown. This large, retrospective, observational study assessed QoL in people transitioning to device-aided therapy (deep brain stimulation or carbidopa-levodopa enteral suspension) vs. those continuing oral medications. Cohorts were matched based on clinical/demographic characteristics and device-aided therapy eligibility. Primary and secondary outcomes included change from baseline (CFB) to month 12 in 39-item Parkinson’s Disease Questionnaire (PDQ-39) and Unified Parkinson’s Disease Rating Scale (UPDRS) scores, respectively. Of 608 people (oral therapy [n = 295]; device-aided therapy [n = 313]), most were male, White, and aged ≥ 60 years. Positive CFB to month 12 in PDQ-39 was significantly greater for device-aided therapy vs. oral therapy (–5.0 [95% CI, –5.9 to –4.2] vs. 0.9 [0.3–1.5]; p < 0.001). UPDRS II-IV scores improved for the device-aided therapy group. People transitioning to device-aided therapy experienced clinically meaningful QoL improvements.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"7 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Urea cycle dysregulation drives metabolic stress and neurodegeneration in Parkinson’s disease 尿素循环失调驱动帕金森病的代谢应激和神经变性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-11 DOI: 10.1038/s41531-025-01099-5

Shengyao Zhang, Guoran Wan, Yu Qiu, Meng Zhang, Hongmei Deng, Qiongfang Wang, Junyi Hu, Jie Gui, Dilong Chen, Boyue Huang, Jianhua Ran

{"title":"Urea cycle dysregulation drives metabolic stress and neurodegeneration in Parkinson’s disease","authors":"Shengyao Zhang, Guoran Wan, Yu Qiu, Meng Zhang, Hongmei Deng, Qiongfang Wang, Junyi Hu, Jie Gui, Dilong Chen, Boyue Huang, Jianhua Ran","doi":"10.1038/s41531-025-01099-5","DOIUrl":"https://doi.org/10.1038/s41531-025-01099-5","url":null,"abstract":"Parkinson’s disease (PD), common neurodegenerative disorder, involves substantia nigra dopaminergic neuron loss and α-synuclein accumulation in Lewy bodies. While pathogenesis remains unclear, dysregulated urea metabolism may play a central role. This study detected elevated serum urea levels in PD patients with upregulated urea cycle enzymes. In MPTP-induced PD mice, urea accumulated in the substantia nigra and striatum, alongside increased activity of urea cycle enzymes (ODC1, ARG1, OTC) and urea transporter UT-B. Mechanistically, brain urea accumulation likely stems from imbalanced urea cycle activity and impaired UT-B-mediated clearance, with compensatory UT-B upregulation specifically in the substantia nigra. In vitro, MPTP-treated neuronal cells showed increased enzyme and UT-B expression, while high urea directly suppressed tyrosine hydroxylase (TH). Importantly, ODC1 knockdown reversed urea dysmetabolism, restored TH, and alleviated neuronal damage. These findings establish ODC1-mediated urea cycle dysregulation as a core metabolic feature of PD, proposing ODC1 or urea metabolism as novel therapeutic targets.<figure></figure>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"18 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Strain-specific effects of Desulfovibrio on neurodegeneration and oxidative stress in a Caenorhabditis elegans PD model 在秀丽隐杆线虫PD模型中，Desulfovibrio对神经变性和氧化应激的菌株特异性影响

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-11 DOI: 10.1038/s41531-025-01102-z

Khosrow Mohammadi, Dongming Zhang, Per Erik Joakim Saris

{"title":"Strain-specific effects of Desulfovibrio on neurodegeneration and oxidative stress in a Caenorhabditis elegans PD model","authors":"Khosrow Mohammadi, Dongming Zhang, Per Erik Joakim Saris","doi":"10.1038/s41531-025-01102-z","DOIUrl":"https://doi.org/10.1038/s41531-025-01102-z","url":null,"abstract":"The gut microbiota is increasingly recognized as a key contributor to intestinal and brain pathologies, including Parkinson’s disease (PD). Sulfate-reducing Desulfovibrio (DSV) species have emerged as microbial drivers through hydrogen sulfide and other neurotoxic factors. Using the Caenorhabditis elegans PD model NL5901 expressing human α-synuclein, we examined the effects of six DSV strains from human, animal, and environmental sources on food preference, α-syn aggregation, ROS production, gene expression, and lifespan. C. elegans strongly preferred environmental strains, particularly D. vulgaris DSM 644 (94.7% vs. 5.3% over D. piger DSM 749). In contrast, the animal isolate D. desulfuricans DSM 6949 and PD isolate D. spp. MUU 26 induced the highest α-syn aggregation (49.05 and 40.15 aggregates), ROS (3.42-fold, 3.01-fold), and sod-3, daf-16, and hsp-16.1 repression. DSM 644-fed worms exhibited a protective transcriptional profile and the greatest lifespan extension (median 36 days). These results highlight strain-specific effects of DSV on neurodegeneration, oxidative stress, and aging, reinforcing the need for mechanistic validation in mammalian PD models.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"3 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Towards scalable screening for the early detection of Parkinson’s disease: validation of an iPad-based eye movement assessment system against a clinical-grade eye tracker 迈向可扩展的帕金森病早期检测筛查：基于ipad的眼动评估系统与临床级眼动仪的验证

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-08 DOI: 10.1038/s41531-025-01079-9

Jamie Koerner, Erin Zou, Jessica A. Karl, Cynthia Poon, Leo Verhagen Metman, Charles G. Sodini, Vivienne Sze, Fabian J. David, Thomas Heldt

{"title":"Towards scalable screening for the early detection of Parkinson’s disease: validation of an iPad-based eye movement assessment system against a clinical-grade eye tracker","authors":"Jamie Koerner, Erin Zou, Jessica A. Karl, Cynthia Poon, Leo Verhagen Metman, Charles G. Sodini, Vivienne Sze, Fabian J. David, Thomas Heldt","doi":"10.1038/s41531-025-01079-9","DOIUrl":"https://doi.org/10.1038/s41531-025-01079-9","url":null,"abstract":"Early detection and monitoring of Parkinson’s disease (PD) remain challenging, highlighting the need for accessible, cost-effective tools. Saccadic eye movement abnormalities are promising noninvasive biomarkers for PD screening and monitoring. Here, we present an iPad-based system that uses a deep learning algorithm to extract saccade metrics and validate these metrics against the clinical-grade EyeLink 1000 Plus. Twenty-five participants (10 with PD, 15 controls) completed pro-saccade, anti-saccade, memory-guided-saccade, and self-generated-saccade tasks. Relative to the EyeLink, the iPad system achieved average subject-level errors of 2 ms for latency and 0.7∘ for amplitude in pro-, anti-, and memory-guided saccades, and 0.003 s−1 for inter-saccadic rate and 1.6∘ for amplitude in self-generated saccades. A review of 22 studies on PD-related saccadic impairments established benchmarks for clinically meaningful effects. The iPad-based system meets or exceeds these benchmarks, supporting its use as a scalable and cost-effective tool for screening and monitoring PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"70 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Online prediction of optimal deep brain stimulation contacts from local field potentials in Parkinson's disease. 帕金森病患者局部场电位的最佳脑深部刺激接触在线预测。

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-08 DOI: 10.1038/s41531-025-01092-y

Marjolein Muller,Stefano Scafa,Ibrahem Hanafi,Camille Varescon,Chiara Palmisano,Saskia van der Gaag,Rodi Zutt,Niels A van der Gaag,Carel F E Hoffmann,Jocelyne Bloch,Mayte Castro Jiménez,Julien F Bally,Philipp Capetian,Ioannis U Isaias,Eduardo M Moraud,M Fiorella Contarino

{"title":"Online prediction of optimal deep brain stimulation contacts from local field potentials in Parkinson's disease.","authors":"Marjolein Muller,Stefano Scafa,Ibrahem Hanafi,Camille Varescon,Chiara Palmisano,Saskia van der Gaag,Rodi Zutt,Niels A van der Gaag,Carel F E Hoffmann,Jocelyne Bloch,Mayte Castro Jiménez,Julien F Bally,Philipp Capetian,Ioannis U Isaias,Eduardo M Moraud,M Fiorella Contarino","doi":"10.1038/s41531-025-01092-y","DOIUrl":"https://doi.org/10.1038/s41531-025-01092-y","url":null,"abstract":"Selecting optimal contacts for chronic deep-brain stimulation (DBS) requires a monopolar review, involving time-consuming manual testing by trained personnel, often causing patient discomfort. Neural biomarkers, such as local field potentials (LFP), could streamline this process. This study aimed to validate LFP recordings from chronically implanted neurostimulators for guiding clinical contact-level selection. We retrospectively analysed bipolar LFP recordings from Parkinson's disease patients across three centres (Netherlands: 68, Switzerland: 21, Germany: 32). Using beta-band power measures (13-35 Hz), we ranked channels based on clinical contact-level choices and developed two prediction algorithms: (i) a \"decision tree\" method for in-clinic use and (ii) a \"pattern based\" method for offline validation. The \"decision tree\" method achieved accuracies of 86.5% (NL), 86.7% (CH), and 75.0% (DE) for predicting the top two contact-levels. Both methods outperformed an existing algorithm. These findings suggest LFP-based approaches can enhance DBS programming efficiency, potentially reducing patient burden and clinical workload.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"12 1","pages":"234"},"PeriodicalIF":8.7,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy 脑脊液和血浆α-突触核蛋白磷酸化不反映突触核蛋白病

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-07 DOI: 10.1038/s41531-025-01086-w

Giovanni Bellomo, Erik Stoops, Jeroen Vanbrabant, Leentje Demeyer, Cindy Francois, Melanie Vanhooren, Yihua Ma, Carly M. Farris, Luis Concha-Marambio, Federico Paolini Paoletti, Lorenzo Gaetani, Lucilla Parnetti, Davide Chiasserini

{"title":"Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy","authors":"Giovanni Bellomo, Erik Stoops, Jeroen Vanbrabant, Leentje Demeyer, Cindy Francois, Melanie Vanhooren, Yihua Ma, Carly M. Farris, Luis Concha-Marambio, Federico Paolini Paoletti, Lorenzo Gaetani, Lucilla Parnetti, Davide Chiasserini","doi":"10.1038/s41531-025-01086-w","DOIUrl":"https://doi.org/10.1038/s41531-025-01086-w","url":null,"abstract":"We developed a highly sensitive and specific single-molecule array (Simoa) Homebrew assay for quantification of phosphorylated α-synuclein at serine 129 (pS129 α-syn) and evaluated its performance in human cerebrospinal fluid (CSF) and plasma. Using a cohort of patients with Parkinson’s disease (PD), Alzheimer’s disease (AD), and neurological controls with available CSF α-synuclein seed amplification assay (synSAA) outcome, we examined pS129 α-syn alongside N-terminal and C-terminal α-syn proteoforms. Our results showed that pS129 α-syn concentration was about 1% and 0.001% of the other α-syn species in CSF and plasma, respectively. We found no correlation between pS129 α-syn and synSAA outcome, indicating that soluble pS129 α-syn in CSF and plasma does not reflect presence of synucleinopathy. Interestingly, pS129 α-syn and other α-syn forms were significantly increased in AD compared to PD and controls, supporting the role of α-syn as biomarker of synaptic degeneration in AD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"1 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Regulation of polyamine interconversion enzymes affects α-Synuclein levels and toxicity in a Drosophila model of Parkinson’s Disease 在帕金森病的果蝇模型中，多胺相互转换酶的调节影响α-突触核蛋白水平和毒性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-06 DOI: 10.1038/s41531-025-01087-9

Bedri Ranxhi, Zoya R. Bangash, Zachary M. Chbihi, Zaina Qadri, Nazin N. Islam, Sokol V. Todi, Peter A. LeWitt, Wei-Ling Tsou

{"title":"Regulation of polyamine interconversion enzymes affects α-Synuclein levels and toxicity in a Drosophila model of Parkinson’s Disease","authors":"Bedri Ranxhi, Zoya R. Bangash, Zachary M. Chbihi, Zaina Qadri, Nazin N. Islam, Sokol V. Todi, Peter A. LeWitt, Wei-Ling Tsou","doi":"10.1038/s41531-025-01087-9","DOIUrl":"https://doi.org/10.1038/s41531-025-01087-9","url":null,"abstract":"Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by α-synuclein accumulation and aggregation, leading to disrupted cellular homeostasis, impaired mitochondrial function, and neuroinflammation, ultimately causing neuronal death. Recent biomarker studies reveal elevated serum levels of L-ornithine-derived polyamines correlating with PD progression and clinical subtypes, though their precise role in PD pathology remains unclear. We investigated the impact of polyamine-interconversion enzymes (PAIEs) on α-synucleinopathy in a Drosophila melanogaster model of PD, evaluating key degenerative features such as lifespan, locomotor function, tissue integrity, and α-synuclein accumulation. Knockdown of ornithine decarboxylase 1 (ODC1), spermidine synthase (SRM), and spermine oxidase (SMOX) reduced α-synuclein toxicity, while suppression of spermidine/spermine N1-acetyltransferase 1 (SAT1) and spermine synthase (SMS) exacerbated it. Conversely, overexpressing SAT1 or SMOX significantly reduced α-synuclein toxicity, highlighting their potential role in PD. These findings underscore the critical role of polyamine pathways in modulating α-synuclein toxicity, offering novel therapeutic targets for PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"6 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Enhanced beta power emerges from simulated parkinsonian primary motor cortex 增强的β能量从模拟帕金森初级运动皮层出现

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-05 DOI: 10.1038/s41531-025-01070-4

Donald W. Doherty, Liqiang Chen, Yoland Smith, Thomas Wichmann, Hong-Yuan Chu, William W. Lytton

引用次数: 0

GABA outperforms iron and neuromelanin in detecting nigrostriatal alterations in early-stage Parkinson’s disease with RBD GABA在检测早期帕金森病伴RBD的黑质纹状体改变方面优于铁和神经黑色素

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-08-05 DOI: 10.1038/s41531-025-01096-8

Youmin Zhang, Pei Huang, Peng Liu, Yan Li, Zhijia Jin, Qiurong Yu, Xiaofeng Shi, Yu Liu, Zenghui Cheng, Peng Wu, Jinyuan Weng, Fangtao Liu, Ewart Mark Haacke, Ying Cui, Shengdi Chen, Naying He, Fuhua Yan

引用次数: 0