NPJ Parkinson's Disease最新文献_第9页

Biologically defined neuronal synuclein disease as a tool to advance drug development 将生物定义的神经元突触核蛋白疾病作为推动药物开发的工具

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-12-20 DOI: 10.1038/s41531-024-00845-5

Gennaro Pagano, Tien Dam, Geoffrey A. Kerchner, Wendy R. Galpern, Milton Biagioni, Rajesh Karan, Danna Jennings, M. Judith Peterschmitt, Tania Nikolcheva, Patrik Brundin

引用次数: 0

Multimodal oculomotor assessment reveals prodromal markers of Parkinson’s disease in non-manifesting LRRK2 G2019S mutation carriers 多模式动眼力评估揭示了未表现出LRRK2 G2019S突变携带者帕金森病的前驱症状标志物

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-12-19 DOI: 10.1038/s41531-024-00840-w

Heidi C. Riek, Naomi P. Visanji, Isabell C. Pitigoi, Daniel G. Di Luca, Laura Armengou-Garcia, Nazish Ahmed, Julia E. Perkins, Donald C. Brien, Jeff Huang, Brian C. Coe, Jana Huang, Taneera Ghate, Anthony E. Lang, Connie Marras, Douglas P. Munoz

{"title":"Multimodal oculomotor assessment reveals prodromal markers of Parkinson’s disease in non-manifesting LRRK2 G2019S mutation carriers","authors":"Heidi C. Riek, Naomi P. Visanji, Isabell C. Pitigoi, Daniel G. Di Luca, Laura Armengou-Garcia, Nazish Ahmed, Julia E. Perkins, Donald C. Brien, Jeff Huang, Brian C. Coe, Jana Huang, Taneera Ghate, Anthony E. Lang, Connie Marras, Douglas P. Munoz","doi":"10.1038/s41531-024-00840-w","DOIUrl":"https://doi.org/10.1038/s41531-024-00840-w","url":null,"abstract":"Oculomotor behaviour changes in patients with Parkinson’s disease (PD) are a promising source of prodromal disease markers. Capitalizing on this phenomenon to facilitate early diagnosis requires oculomotor assessment in prodromal cohorts. We examined oculomotor behaviour in non-manifesting LRRK2 G2019S mutation carriers (LRRK2-NM), who have heightened PD risk.Seventeen LRRK2-NM participants, 47 patients with idiopathic PD, and 63 healthy age-matched control participants completed an interleaved pro- and antisaccade task while undergoing video-based eye-tracking. We analyzed between-group differences in saccade, pupil, blink, and fixation acquisition behaviour. Patients with PD showed previously demonstrated abnormalities (saccade hypometria, antisaccade errors). Relative to controls, LRRK2-NM participants and patients with PD both displayed increased short-latency prosaccades and reduced pupil velocity, plus altered fixation acquisition—less preemptive returning of gaze to the future fixation point location. Interestingly, the effect on blink probability was opposite—higher than controls in LRRK2-NM participants but lower in patients with PD. Future longitudinal studies must confirm the viability of these features as prodromal PD markers.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"47 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849099","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

Mitochondrial oxidant stress promotes α-synuclein aggregation and spreading in mice with mutated glucocerebrosidase 线粒体氧化应激促进糖脑苷酶突变小鼠α-突触核蛋白聚集和扩散

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-12-11 DOI: 10.1038/s41531-024-00842-8

Pietro La Vitola, Eva M. Szegö, Rita Pinto-Costa, Angela Rollar, Eugenia Harbachova, Anthony HV Schapira, Ayse Ulusoy, Donato A. Di Monte

{"title":"Mitochondrial oxidant stress promotes α-synuclein aggregation and spreading in mice with mutated glucocerebrosidase","authors":"Pietro La Vitola, Eva M. Szegö, Rita Pinto-Costa, Angela Rollar, Eugenia Harbachova, Anthony HV Schapira, Ayse Ulusoy, Donato A. Di Monte","doi":"10.1038/s41531-024-00842-8","DOIUrl":"https://doi.org/10.1038/s41531-024-00842-8","url":null,"abstract":"In this study, heterozygous expression of a common Parkinson-associated GBA1 variant, the L444P mutation, was found to exacerbate α-synuclein aggregation and spreading in a mouse model of Parkinson-like pathology targeting neurons of the medullary vagal system. These neurons were also shown to become more vulnerable to oxidative and nitrative stress after L444P expression. The latter paralleled neuronal formation of reactive oxygen species and led to a pronounced accumulation of nitrated α-synuclein. A causal relationship linked mutation-induced oxidative/nitrative stress to enhanced α-synuclein aggregation and spreading that could indeed be rescued by neuronal overexpression of mitochondrial superoxide dismutase 2. Further evidence supported a key involvement of mitochondria as sources of reactive oxygen species as well as targets of oxidative and nitrative damage within L444P-expressing neurons. These findings support the conclusion that enhanced vulnerability to mitochondrial oxidative stress should be considered an important mechanism predisposing to pathology conversion in carriers of GBA1 mutations.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804534","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

Bidirectional relationship between olfaction and Parkinson’s disease 嗅觉与帕金森病的双向关系

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-12-05 DOI: 10.1038/s41531-024-00838-4

Jonggeol Jeffrey Kim, Sara Bandres-Ciga, Karl Heilbron, Cornelis Blauwendraat, Alastair J. Noyce

引用次数: 0

Comparison of vagus nerve cross-sectional area between brain-first and body-first Parkinson’s disease 脑先与体先帕金森病迷走神经横截面积的比较

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-12-05 DOI: 10.1038/s41531-024-00844-6

Shuangshuang Dong, Bo Shen, Xu Jiang, Jun Zhu, Haiying Zhang, Yang Zhao, Yaning Chen, Dongfeng Li, Yuanyuan Feng, Yi Chen, Yang Pan, Feng Han, Ben Liu, Li Zhang

引用次数: 0

MRgFUS subthalamotomy in Parkinson’s disease: an approach aimed at minimizing Lesion Volume 帕金森病的MRgFUS丘脑下切开术：旨在减少病变体积的方法

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-12-02 DOI: 10.1038/s41531-024-00843-7

Marina Campins-Romeu, Rebeca Conde-Sardón, Isabel Sastre-Bataller, Carlos Morata-Martínez, Mireya Losada-López, José Luís León-Guijarro, Luis Raga-Rodríguez, Julia Pérez-García, Antonio Gutiérrez-Martín, Andrés M. Lozano, Raquel Baviera-Muñoz, Irene Martínez-Torres

{"title":"MRgFUS subthalamotomy in Parkinson’s disease: an approach aimed at minimizing Lesion Volume","authors":"Marina Campins-Romeu, Rebeca Conde-Sardón, Isabel Sastre-Bataller, Carlos Morata-Martínez, Mireya Losada-López, José Luís León-Guijarro, Luis Raga-Rodríguez, Julia Pérez-García, Antonio Gutiérrez-Martín, Andrés M. Lozano, Raquel Baviera-Muñoz, Irene Martínez-Torres","doi":"10.1038/s41531-024-00843-7","DOIUrl":"https://doi.org/10.1038/s41531-024-00843-7","url":null,"abstract":"Idiopathic Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and postural instability. Magnetic Resonance-guided high-intensity focused ultrasound (MRgFUS) of the subthalamic nucleus (STN) is gaining recognition as a minimally invasive surgical option. This study assesses the safety and efficacy of unilateral MRgFUS subthalamotomy, aiming to create the smallest effective lesion. Between June 2021 and October 2023, twelve PD patients underwent the procedure, with primary outcomes focused on safety and motor improvements after six months. Results indicated significant motor improvements, with over 50% reduction in tremor, rigidity, and bradykinesia, while balance and gait remained stable. Quality of life also improved. Side effects were generally mild and transient, though some patients experienced involuntary movements, managed through medication adjustments. Despite limitations, this technique appears to offer a promising, less-invasive alternative for managing PD symptoms with a favorable risk-benefit profile. Further research is necessary to refine the procedure and assess long-term outcomes.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"75 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760486","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

Personalized progression modelling and prediction in Parkinson’s disease with a novel multi-modal graph approach 一种新的多模态图方法在帕金森病的个性化进程建模和预测

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-12-01 DOI: 10.1038/s41531-024-00832-w

Jie Lian, Xufang Luo, Caihua Shan, Dongqi Han, Chencheng Zhang, Varut Vardhanabhuti, Dongsheng Li, Lili Qiu

{"title":"Personalized progression modelling and prediction in Parkinson’s disease with a novel multi-modal graph approach","authors":"Jie Lian, Xufang Luo, Caihua Shan, Dongqi Han, Chencheng Zhang, Varut Vardhanabhuti, Dongsheng Li, Lili Qiu","doi":"10.1038/s41531-024-00832-w","DOIUrl":"https://doi.org/10.1038/s41531-024-00832-w","url":null,"abstract":"Parkinson’s disease (PD) is a complex neurological disorder characterized by dopaminergic neuron degeneration, leading to diverse motor and non-motor impairments. This variability complicates accurate progression modelling and early-stage prediction. Traditional classification methods based on clinical symptoms are often limited by disease heterogeneity. This study introduces an graph-based interpretable personalized progression method, utilizing data from the Parkinson’s Progression Markers Initiative (PPMI) and Stroke Parkinson’s Disease Biomarker Program (PDBP). Our approach integrates multimodal inter-individual and intra-individual data, including clinical assessments, MRI, and genetic information to make multi-dimension predictions. Validated using the PDBP dataset from 12 to 36 months, our AdaMedGraph method demonstrated strong performance, achieving AUC values of 0.748 and 0.714 for the 12-month Hoehn and Yahr Scale and Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III on the PPMI test set. Ablation analysis reveals the importance of baseline clinical assessment predictors. This novel framework improves personalized care and offers insights into unique disease trajectories in PD patients.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"18 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756349","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

Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson’s Disease 左旋多巴诱导帕金森病运动障碍的分子和细胞决定因素

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-30 DOI: 10.1038/s41531-024-00836-6

Federica Servillo, Maria De Carluccio, Giulia Di Lazzaro, Federica Campanelli, Gioia Marino, Giuseppina Natale, Ada Ledonne, Mariangela Massaro Cenere, Emanuela Paldino, Daniela Di Giuda, Anna Picca, Francesco Bove, Riccardo Di Iorio, Benedetta Angeloni, Angelo Tiziano Cimmino, Giovanni Bellomo, Barbara Picconi, Anna Rita Bentivoglio, Nicola Biagio Mercuri, Lucilla Parnetti, Veronica Ghiglieri, Maria Teresa Viscomi, Paolo Calabresi

{"title":"Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson’s Disease","authors":"Federica Servillo, Maria De Carluccio, Giulia Di Lazzaro, Federica Campanelli, Gioia Marino, Giuseppina Natale, Ada Ledonne, Mariangela Massaro Cenere, Emanuela Paldino, Daniela Di Giuda, Anna Picca, Francesco Bove, Riccardo Di Iorio, Benedetta Angeloni, Angelo Tiziano Cimmino, Giovanni Bellomo, Barbara Picconi, Anna Rita Bentivoglio, Nicola Biagio Mercuri, Lucilla Parnetti, Veronica Ghiglieri, Maria Teresa Viscomi, Paolo Calabresi","doi":"10.1038/s41531-024-00836-6","DOIUrl":"https://doi.org/10.1038/s41531-024-00836-6","url":null,"abstract":"Treatment with L-3,4-dihydroxyphenylalanine (L-Dopa) compensates for decreased striatal dopamine (DA) levels and reduces Parkinson’s disease (PD) symptoms. However, during disease progression, L-Dopa-induced dyskinesia (LID) develops virtually in all PD patients, making the control of PD symptoms difficult. Thus, understanding the mechanisms underlying LID and the control of these motor abnormalities is a major issue in the care of PD patients. From experimental and clinical studies, a complex cascade of molecular and cellular events emerges, but the primary determinants of LID are still unclear. Here, with a translational approach, including four animal models and a wide cohort of PD patients, we show that striatal DA denervation is the major causal factor for the emergence of LID, while α-synuclein aggregates do not seem to play a significant role. Our data also support the concept that maladaptive basal ganglia plasticity is the main pathophysiological mechanism underlying LID.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"26 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756301","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

MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity MJF-14接近结扎法检测早期非包涵性α -突触核蛋白病理，具有增强的特异性和敏感性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-29 DOI: 10.1038/s41531-024-00841-9

Nanna Møller Jensen, YuHong Fu, Cristine Betzer, Hongyun Li, Sara Elfarrash, Ali H. Shaib, Donatus Krah, Zagorka Vitic, Lasse Reimer, Hjalte Gram, Vladimir Buchman, Mark Denham, Silvio O. Rizzoli, Glenda M. Halliday, Poul Henning Jensen

{"title":"MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity","authors":"Nanna Møller Jensen, YuHong Fu, Cristine Betzer, Hongyun Li, Sara Elfarrash, Ali H. Shaib, Donatus Krah, Zagorka Vitic, Lasse Reimer, Hjalte Gram, Vladimir Buchman, Mark Denham, Silvio O. Rizzoli, Glenda M. Halliday, Poul Henning Jensen","doi":"10.1038/s41531-024-00841-9","DOIUrl":"https://doi.org/10.1038/s41531-024-00841-9","url":null,"abstract":"α-Synuclein proximity ligation assay (PLA) has proved a sensitive technique for detection of non-Lewy body α-synuclein aggregate pathology. Here, we describe the MJF-14 PLA, a new PLA towards aggregated α-synuclein with unprecedented specificity, using the aggregate-selective α-synuclein antibody MJFR-14-6-4-2 (hereafter MJF-14). Signal in the assay correlates with α-synuclein aggregation in cell culture and human neurons, induced by α-synuclein overexpression or pre-formed fibrils. Co-labelling of MJF-14 PLA and pS129-α-synuclein immunofluorescence in post-mortem cases of dementia with Lewy bodies shows that while the MJF-14 PLA reveals extensive non-inclusion pathology, it is not sensitive towards pS129-α-synuclein-positive Lewy bodies. In Parkinson’s disease brain, direct comparison of PLA and immunohistochemistry with the MJF-14 antibody shows widespread α-synuclein pathology preceding the formation of conventional Lewy pathology. In conclusion, we introduce an improved α-synuclein aggregate PLA to uncover abundant non-inclusion pathology, which deserves future validation with brain bank resources and in different synucleinopathies.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142753741","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

Awake versus asleep deep brain stimulation targeting the caudal zona incerta for essential tremor 针对尾椎内侧的深部脑刺激治疗本质性震颤

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-22 DOI: 10.1038/s41531-024-00833-9

Rasmus Stenmark Persson, Yulia Blomstedt, Anders Fytagoridis, Marwan Hariz, Patric Blomstedt

{"title":"Awake versus asleep deep brain stimulation targeting the caudal zona incerta for essential tremor","authors":"Rasmus Stenmark Persson, Yulia Blomstedt, Anders Fytagoridis, Marwan Hariz, Patric Blomstedt","doi":"10.1038/s41531-024-00833-9","DOIUrl":"https://doi.org/10.1038/s41531-024-00833-9","url":null,"abstract":"To compare awake and asleep deep brain stimulation (DBS) surgery for Essential Tremor (ET), we conducted this retrospective cohort study of patients consecutively operated with DBS targeting the caudal Zona incerta (cZi). 37 underwent surgery awake and 55 asleep. Tremor before surgery and on/off stimulation one year after surgery were evaluated using the Essential Tremor Rating Scale (ETRS). Procedural time, electrode localization, stimulation parameters and adverse events were noted and compared. ETRS scores were similar at baseline between the groups except for contralateral arm tremor, which was slightly worse in the awake group. Total ETRS, contralateral arm tremor and activities of daily living scores showed no significant difference between the groups on-stimulation at one-year follow-up. Compared to the awake group, the asleep group had shorter procedural time and lower stimulation parameters. There were no intracranial haemorrhages nor surgery site-infections. Both groups showed a good improvement of tremor at one-year follow-up. Image-guided DBS surgery targeting the cZi enables safe and efficient asleep surgery for ET.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"36 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684149","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