NPJ Parkinson's Disease最新文献_第2页

Systematic review and consensus conceptual model of meaningful symptoms and functional impacts in early Parkinson’s Disease 早期帕金森病有意义症状和功能影响的系统回顾和共识概念模型

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-03 DOI: 10.1038/s41531-025-00907-2

Jennifer R. Mammen, Jamie L. Adams, Rikki Mangrum, Yuge Xiao, William Barbosa, Mirinda Tyo, Christopher Redmond, Cheryl Carter, Kelly Cifelli, Robert Cifelli, Hope Maruzo, Jim Meeker, Gerry Shultz, Colbren Thomas, Claire Bale, Evan Davies, Catherine M. Kopil, Connie Marras, Tiago Mestre, Thomas Morel, Tanya Simuni, Glenn T. Stebbins, Daniel Weintraub, Diane Stephenson

{"title":"Systematic review and consensus conceptual model of meaningful symptoms and functional impacts in early Parkinson’s Disease","authors":"Jennifer R. Mammen, Jamie L. Adams, Rikki Mangrum, Yuge Xiao, William Barbosa, Mirinda Tyo, Christopher Redmond, Cheryl Carter, Kelly Cifelli, Robert Cifelli, Hope Maruzo, Jim Meeker, Gerry Shultz, Colbren Thomas, Claire Bale, Evan Davies, Catherine M. Kopil, Connie Marras, Tiago Mestre, Thomas Morel, Tanya Simuni, Glenn T. Stebbins, Daniel Weintraub, Diane Stephenson","doi":"10.1038/s41531-025-00907-2","DOIUrl":"https://doi.org/10.1038/s41531-025-00907-2","url":null,"abstract":"A comprehensive, patient-centered conceptual model of early Parkinson’s is lacking and is greatly needed. A systematic review and meta-synthesis of qualitative and quantitative research was conducted by a multi-stakeholder taskforce using JBI Mixed Methods Review criteria and GRADE-CERQual standards for assessment of evidence. Over 340 symptoms and impacts were identified across ten symptom domains (Movement, Cognitive, Psychiatric, Sleep, Sensory, Speech, Digestive, Urinary, Sexual, Autonomic) and two impact domains (Physical and Psychosocial functioning). A wide range of motor and non-motor symptoms were present in early disease, with strongest support for tremor, dexterity, gait, stiffness, slow movements, cognitive, mood, and sleep alterations, urinary dysfunction, constipation, pain, and fatigue. These affected mobility, self-concept, coping, effort of living, interactions and important activities, with evidence of many understudied concepts. This model offers the most comprehensive catalogue of symptoms and impacts in Parkinson’s to date and will support clinical practice and endpoint selection for therapeutic trials.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"107 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766626","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

Predictive modeling to uncover Parkinson’s disease characteristics that delay diagnosis

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-02 DOI: 10.1038/s41531-025-00923-2

Tom Hähnel, Tamara Raschka, Jochen Klucken, Enrico Glaab, Jean-Christophe Corvol, Björn H. Falkenburger, Holger Fröhlich

引用次数: 0

Deciphering shared molecular dysregulation across Parkinson’s disease variants using a multi-modal network-based data integration and analysis

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-31 DOI: 10.1038/s41531-025-00914-3

Alise Zagare, Irina Balaur, Adrien Rougny, Claudia Saraiva, Matthieu Gobin, Anna S. Monzel, Soumyabrata Ghosh, Venkata P. Satagopam, Jens C. Schwamborn

{"title":"Deciphering shared molecular dysregulation across Parkinson’s disease variants using a multi-modal network-based data integration and analysis","authors":"Alise Zagare, Irina Balaur, Adrien Rougny, Claudia Saraiva, Matthieu Gobin, Anna S. Monzel, Soumyabrata Ghosh, Venkata P. Satagopam, Jens C. Schwamborn","doi":"10.1038/s41531-025-00914-3","DOIUrl":"https://doi.org/10.1038/s41531-025-00914-3","url":null,"abstract":"Parkinson’s disease (PD) is a progressive neurodegenerative disorder with no effective treatment. Advances in neuroscience and systems biomedicine now enable the use of complex patient-specific in vitro disease models and cutting-edge computational tools for data integration, enhancing our understanding of complex PD mechanisms. To explore common biomedical features across monogenic PD forms, we developed a knowledge graph (KG) by integrating previously published high-content imaging and RNA sequencing data of PD patient-specific midbrain organoids harbouring LRRK2-G2019S, SNCA triplication, GBA-N370S or MIRO1-R272Q mutations with publicly available biological data. Furthermore, we generated a single-cell RNA sequencing dataset of midbrain organoids derived from idiopathic PD patients (IPD) to stratify IPD patients within the spectrum of monogenic forms of PD. Despite the high degree of PD heterogeneity, we found that common transcriptomic dysregulation in monogenic PD forms is reflected in glial cells of IPD patient midbrain organoids. In addition, dysregulation in ROBO signalling might be involved in shared pathophysiology between monogenic PD and IPD cases.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"12 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745575","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

The homozygous LRRK2.p.N1437D point mutation mouse is a novel model of parkinsonism

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-28 DOI: 10.1038/s41531-025-00905-4

Lin-Hua Gan, Yi-Min Sun, Xin-Yue Zhou, Zhi-Yuan Qi, Feng-Tao Liu, Yi-Lin Tang, Wen-bo Yu, Bao-Guo Xiao, Jian Wang, Jian-Jun Wu

{"title":"The homozygous LRRK2.p.N1437D point mutation mouse is a novel model of parkinsonism","authors":"Lin-Hua Gan, Yi-Min Sun, Xin-Yue Zhou, Zhi-Yuan Qi, Feng-Tao Liu, Yi-Lin Tang, Wen-bo Yu, Bao-Guo Xiao, Jian Wang, Jian-Jun Wu","doi":"10.1038/s41531-025-00905-4","DOIUrl":"https://doi.org/10.1038/s41531-025-00905-4","url":null,"abstract":"The leucine-rich repeat kinase 2 (LRRK2) gene is one of the most common genetic causes of autosomal dominant Parkinson’s disease (PD) and a common genetic risk factor for sporadic PD. However, aged mice with common LRRK2 point mutations fail to exhibit age-related PD-associated behavioral and pathological impairments. We generated a novel mouse model harboring the LRRK2.p.N1437D point mutation (c.4309 A > G; NM_98578). Here, the homozygous N1437D mutation, but not the heterozygous mutation, led to an increase in the autophosphorylation, substrate phosphorylation, and GTP-binding capacity of LRRK2. Heterozygous N1437D mice also showed unaffected behavior and pathology while the homozygous mice exhibited PD-associated behavioral change at 25–26 months, dopamine system damage, lipofuscin accumulation, and lipid peroxidation in substantia nigra dopaminergic neurons at 26–27 months. The new N1437D point mutation mouse does not require LRRK2 overexpression and may better mimic the pathological characteristics of LRRK2 mutation in the ROC-COR region.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"63 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723449","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

Association of glymphatic system function with peripheral inflammation and motor symptoms in Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-28 DOI: 10.1038/s41531-025-00909-0

Ruolan Lin, Guoen Cai, Ying Chen, Jinmei Zheng, Shu Wang, Huinan Xiao, Qinyong Ye, Yunjing Xue, Rifeng Jiang

{"title":"Association of glymphatic system function with peripheral inflammation and motor symptoms in Parkinson’s disease","authors":"Ruolan Lin, Guoen Cai, Ying Chen, Jinmei Zheng, Shu Wang, Huinan Xiao, Qinyong Ye, Yunjing Xue, Rifeng Jiang","doi":"10.1038/s41531-025-00909-0","DOIUrl":"https://doi.org/10.1038/s41531-025-00909-0","url":null,"abstract":"Growing evidence highlights the roles of glymphatic system and peripheral inflammation in Parkinson’s disease (PD). We evaluated their interrelationship and potential mechanisms contributing to motor symptoms using DTI-ALPS and inflammatory markers (leukocyte, lymphocyte, neutrophil counts, neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) in 134 PD patients (52 tremor-dominant [TD], 62 postural instability and gait difficulty [PIGD]) and 81 healthy controls (HC, 33 with inflammatory markers). PD exhibited lower DTI-ALPS than HC (1.43 ± 0.19 vs. 1.52 ± 0.21, p = 0.001). DTI-ALPS was negatively correlated with NLR, PLR, and neutrophils in PD (all p < 0.05) and with neutrophils in PIGD (β = –0.043, p = 0.048), and positively correlated with lymphocytes in TD (β = 0.105, p = 0.034). DTI-ALPS mediated the relationship between peripheral inflammation (NLR and neutrophils) and MDS-UPDRS III score in PD. Overall, glymphatic dysfunction correlates with peripheral inflammation and may mediate effects of inflammation on motor symptoms in PD, with distinct inflammation profiles between TD and PIGD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"100 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734063","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

Rotenone induced acute miRNA alterations in extracellular vesicles produce mitochondrial dysfunction and cell death

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-27 DOI: 10.1038/s41531-025-00917-0

Fatema Currim, Josephine Brown-Leung, Tauqeerunnisa Syeda, Matthew Corson, Sofia Schumann, Wenzhu Qi, Priyanka Baloni, Jonathan H. Shannahan, Jean-Christophe Rochet, Rajesh Singh, Jason R. Cannon

{"title":"Rotenone induced acute miRNA alterations in extracellular vesicles produce mitochondrial dysfunction and cell death","authors":"Fatema Currim, Josephine Brown-Leung, Tauqeerunnisa Syeda, Matthew Corson, Sofia Schumann, Wenzhu Qi, Priyanka Baloni, Jonathan H. Shannahan, Jean-Christophe Rochet, Rajesh Singh, Jason R. Cannon","doi":"10.1038/s41531-025-00917-0","DOIUrl":"https://doi.org/10.1038/s41531-025-00917-0","url":null,"abstract":"How extracellular vesicles (EVs) may contribute to mechanisms of primary intracellular pathogenesis in Parkinson’s disease (PD) remains unknown. To critically advance our understanding of how EVs influence early-stage PD pathogenesis, we tested the hypothesis that rats acutely exposed to the PD neurotoxin rotenone would produce differential miRNAs in CSF/serum-derived EVs and that such modulation would be responsible for PD-relevant functional alterations in recipient neuronal cells. We discovered that acute rotenone treatment produced significant and specific serum miRNA alterations. Primary midbrain neurons treated with serum EVs from rotenone-exposed rats produced oxidative stress, mitochondrial toxicity, and cell loss in neuronal culture. These mechanisms were dependent on miR-30a-5p and miR-484. Thus, this study has elucidated that differential expression of miRNAs in circulating EVs from serum/CSF of rats is a potential early diagnostic marker for PD, and that the modulation of cellular functions and viability due to extracellular vesicles determines the pathological fate.<figure></figure>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"125 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712735","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

Innovations and ongoing challenges in digital technologies for Parkinson's disease.

IF 6.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-27 DOI: 10.1038/s41531-025-00920-5

Ryan T Roemmich, Elena Moro, Peter B Shull

引用次数: 0

The LRRK2 p.L1795F variant causes Parkinson’s disease in the European population

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-25 DOI: 10.1038/s41531-025-00896-2

Lara M. Lange, Kristin Levine, Susan H. Fox, Connie Marras, Nazish Ahmed, Nicole Kuznetsov, Dan Vitale, Hirotaka Iwaki, Katja Lohmann, Luca Marsili, Alberto J. Espay, Peter Bauer, Christian Beetz, Jessica Martin, Stewart A. Factor, Lenora A. Higginbotham, Honglei Chen, Hampton Leonard, Mike A. Nalls, Niccolo E. Mencacci, Huw R. Morris, Andrew B. Singleton, Christine Klein, Cornelis Blauwendraat, Zih-Hua Fang

引用次数: 0

Speech and language biomarkers for Parkinson’s disease prediction, early diagnosis and progression

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-24 DOI: 10.1038/s41531-025-00913-4

Fangyuan Cao, Adam P. Vogel, Puya Gharahkhani, Miguel E. Renteria

{"title":"Speech and language biomarkers for Parkinson’s disease prediction, early diagnosis and progression","authors":"Fangyuan Cao, Adam P. Vogel, Puya Gharahkhani, Miguel E. Renteria","doi":"10.1038/s41531-025-00913-4","DOIUrl":"https://doi.org/10.1038/s41531-025-00913-4","url":null,"abstract":"Parkinson’s disease (PD), a multifaceted neurodegenerative disorder, can manifest as an array of motor and non-motor symptoms. Among these, speech and language impairments are particularly prevalent, often preceding motor dysfunctions. Emerging research indicates that these impairments may serve as early disease indicators. In this narrative review, we synthesised current findings on the potential of speech and language symptoms in PD identification and progression monitoring. Our review highlights convergent, albeit preliminary, lines of evidence supporting the value of speech-related features in detecting early or prodromal PD, even across language groups, especially with sophisticated analytical techniques. Distinct speech patterns in PD subtypes and other neurological disorders may assist in differential diagnosis and inform targeted management efforts. These features also evolve over the disease course and could effectively be utilised for disease tracking and guide management plan modifications. Advances in digital voice processing allow cost-effective, remote and scalable monitoring for larger populations.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"35 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677706","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

Voluntary exercise alleviates neural functional deficits in Parkinson’s disease mice by inhibiting microglial ferroptosis via SLC7A11/ALOX12 axis 通过 SLC7A11/ALOX12 轴抑制小胶质细胞铁凋亡，自主运动可减轻帕金森病小鼠的神经功能缺陷

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-23 DOI: 10.1038/s41531-025-00912-5

Jinghui Xu, Xiaofei He, Lili Li, Liying Zhang, Mingyue Li, Yating Mu, Xiaofeng Yang, Shiyin Li, Yifeng Feng, Zejie Zuo, Yunqi Xu, Xiquan Hu, Haiqing Zheng

{"title":"Voluntary exercise alleviates neural functional deficits in Parkinson’s disease mice by inhibiting microglial ferroptosis via SLC7A11/ALOX12 axis","authors":"Jinghui Xu, Xiaofei He, Lili Li, Liying Zhang, Mingyue Li, Yating Mu, Xiaofeng Yang, Shiyin Li, Yifeng Feng, Zejie Zuo, Yunqi Xu, Xiquan Hu, Haiqing Zheng","doi":"10.1038/s41531-025-00912-5","DOIUrl":"https://doi.org/10.1038/s41531-025-00912-5","url":null,"abstract":"Microglia are more susceptible to ferroptosis compared to neurons and astrocytes, which may compromise their phagocytic and clearance capabilities of α-synuclein (α-syn) in Parkinson’s disease (PD). While the beneficial effects of physical exercise (PE) on reducing α-syn deposition in PD have been highlighted, the role of PE in modulating microglial ferroptosis remains unclear. This study focuses on the impact of exercise on inhibiting microglial ferroptosis and mitigating α-syn accumulation. We demonstrate that voluntary exercise effectively inhibits microglial ferroptosis. Mechanistically, PE-induced upregulation of SLC7A11 inhibits microglial ferroptosis by suppressing ALOX12, thereby enhancing microglial phagocytosis and clearance of α-syn, which is paralleled by improvements in neurological function in PD mice. Collectively, these findings not only underscore the critical role of microglial ferroptosis in the pathological progression of PD but also elucidate the molecular mechanism by which PE attenuates microglial ferroptosis via the SLC7A11/ALOX12 axis.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"27 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675219","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