NPJ Parkinson's Disease最新文献_第8页

Disruption of axonal transport in Parkinson’s disease: the role of pathological α-Syn and AMPK/p38 MAPK signaling 帕金森氏病轴突运输的中断：病理性α-Syn和AMPK/p38 MAPK信号的作用

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-06 DOI: 10.1038/s41531-025-00926-z

Xiaoman Yang, Zhuoran Ma, Piaopiao Lian, Yi Wu, Ke Liu, Zhaoyuan Zhang, Zhicheng Tang, Yan Xu, Xuebing Cao

{"title":"Disruption of axonal transport in Parkinson’s disease: the role of pathological α-Syn and AMPK/p38 MAPK signaling","authors":"Xiaoman Yang, Zhuoran Ma, Piaopiao Lian, Yi Wu, Ke Liu, Zhaoyuan Zhang, Zhicheng Tang, Yan Xu, Xuebing Cao","doi":"10.1038/s41531-025-00926-z","DOIUrl":"https://doi.org/10.1038/s41531-025-00926-z","url":null,"abstract":"The accumulation of α-synuclein within Lewy bodies is a critical factor in the pathogenesis of Parkinson’s disease, with potential implications for axonal transport deficits. Activated asparagine endopeptidase enzymatically cleaves α-synuclein and tau, resulting in the formation of α-SynN103 and tauN368, which are markedly elevated in the brains with Parkinson’s disease. In this study, rats received intrastriatal injections of 15 µg of preformed α-SynN103 and tauN368 fibrils, and their behaviors were evaluated after a 2-month period. Subsequent analyses investigated alterations in axonal transport and the underlying molecular mechanisms. Our findings indicated that preformed fibrils reduced kinesin levels and excessively activated the AMPK and p38 MAPK, thereby compromising the function of kinesin and dynein in axonal transport. Pharmacological inhibition of AMPK and p38 MAPK ameliorated these dysfunctions in rat models, which identified Compound C and SB203580 as potent inhibitors, offering evidence for early interventions of Parkinson’s disease.<figure>Mechanisms by which PFFs caused axonal transport defects of dopamine neurons in PD-like models. (A) Shows normal axonal transport. (B) Demonstrates how PFFs increase ?-Syn accumulation, reducing PIKE expression and triggering AMPK/p38 MAPK over-activation, which lowers kinesin levels and motor-cargo interaction. (C) AMPK activity inhibition with C.C significantly improves these deficits. (D) The p38 inhibitor enhances kinesin transport by preventing p38 MAPK over-activation, reducing its inhibition of kinesin-cargo binding.</figure>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"15 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909979","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

Corneal confocal microscopy differentiates patients with secondary parkinsonism from idiopathic Parkinson’s disease 角膜共聚焦显微镜鉴别继发性帕金森病患者和特发性帕金森病患者

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-06 DOI: 10.1038/s41531-025-00969-2

Hong-Qi Yang, Ran Xin, Ning-Ning Che, Qiu-Huan Jiang, Shuai Chen, Si-Yuan Chen, Zhi-Kun Sun, Wei-Min Yang, Xue Li, Jian-Jun Ma, Jie-Wen Zhang, Rayaz A. Malik

{"title":"Corneal confocal microscopy differentiates patients with secondary parkinsonism from idiopathic Parkinson’s disease","authors":"Hong-Qi Yang, Ran Xin, Ning-Ning Che, Qiu-Huan Jiang, Shuai Chen, Si-Yuan Chen, Zhi-Kun Sun, Wei-Min Yang, Xue Li, Jian-Jun Ma, Jie-Wen Zhang, Rayaz A. Malik","doi":"10.1038/s41531-025-00969-2","DOIUrl":"https://doi.org/10.1038/s41531-025-00969-2","url":null,"abstract":"Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra, while secondary parkinsonism (SP) may be due to drugs, vascular, infectious, inflammatory, or even paraneoplastic etiologies. There is currently no biomarker that accurately distinguishes SP from PD. Corneal confocal microscopy (CCM) identifies corneal nerve loss which is associated with motor, cognitive and autonomic dysfunction in PD patients. This study enrolled participants with PD (n = 45) and SP (n = 25). A subset of patients underwent L-6-18F-fluoro-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) scan which showed bilateral decreased dopamine uptake in the putamen and caudate of patients with PD, but not in those with SP. Corneal nerve fiber density (CNFD) (P < 0.001) was lower and corneal nerve branch density (CNBD) (P = 0.007) was higher in the PD group compared to the SP group. The receiver operating characteristic (ROC) analysis revealed that combined CNFD and CNBD showed excellent discrimination between SP and PD, with an area under the curve (AUC) of 0.924. CCM may have clinical utility in differentiating patients with SP from PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"281 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909978","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

Will adaptive deep brain stimulation for Parkinson’s disease become a real option soon? A Delphi consensus study 适应性深部脑刺激治疗帕金森氏症会很快成为一种真正的选择吗？德尔菲共识研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-05 DOI: 10.1038/s41531-025-00974-5

Matteo Guidetti, Tommaso Bocci, Marta De Pedro Del Álamo, Guenther Deuschl, Alfonso Fasano, Raul Martinez-Fernandez, Carmen Gasca-Salas, Clement Hamani, Joachim K. Krauss, Andrea A. Kühn, Patricia Limousin, Simon Little, Andres M. Lozano, Natale V. Maiorana, Sara Marceglia, Michael S. Okun, Serena Oliveri, Jill L. Ostrem, Emma Scelzo, Alfons Schnitzler, Philip A. Starr, Yasin Temel, Lars Timmermann, Gerd Tinkhauser, Veerle Visser-Vandewalle, Jens Volkmann, Alberto Priori

{"title":"Will adaptive deep brain stimulation for Parkinson’s disease become a real option soon? A Delphi consensus study","authors":"Matteo Guidetti, Tommaso Bocci, Marta De Pedro Del Álamo, Guenther Deuschl, Alfonso Fasano, Raul Martinez-Fernandez, Carmen Gasca-Salas, Clement Hamani, Joachim K. Krauss, Andrea A. Kühn, Patricia Limousin, Simon Little, Andres M. Lozano, Natale V. Maiorana, Sara Marceglia, Michael S. Okun, Serena Oliveri, Jill L. Ostrem, Emma Scelzo, Alfons Schnitzler, Philip A. Starr, Yasin Temel, Lars Timmermann, Gerd Tinkhauser, Veerle Visser-Vandewalle, Jens Volkmann, Alberto Priori","doi":"10.1038/s41531-025-00974-5","DOIUrl":"https://doi.org/10.1038/s41531-025-00974-5","url":null,"abstract":"While conventional deep brain stimulation (cDBS) treatment delivers continuous electrical stimuli, new adaptive DBS (aDBS) technology provides dynamic symptom-related stimulation. Research data are promising, and devices are already available, but are we ready for it? We asked leading DBS experts worldwide (n = 21) to discuss a research agenda for aDBS research in the near future to allow full adoption. A 5-point Likert scale questionnaire, along with a Delphi method, was employed. In the next 10 years, aDBS will be clinical routine, but research is needed to define which patients would benefit more from the treatment; second, implantation and programming procedures should be simplified to allow actual generalized adoption; third, new adaptive algorithms, and the integration of aDBS paradigm with new technologies, will improve control of more complex symptoms. Since the next years will be crucial for aDBS implementation, the research should focus on improving precision and making programming procedures more accessible.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"18 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909983","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

New insights into pathogenisis and therapies of P2X7R in Parkinson’s disease P2X7R在帕金森病发病机制和治疗中的新见解

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-05 DOI: 10.1038/s41531-025-00980-7

Shizhuang Wei, Xiaoyu Song, Yakui Mou, Ting Yang, Yao Wang, Hanrui Wang, Chao Ren, Xicheng Song

引用次数: 0

Comparison of oscillatory activity in substantia nigra pars reticulata between Parkinson’s disease and dystonia 帕金森病与肌张力障碍黑质网状部振荡活动的比较

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-05 DOI: 10.1038/s41531-025-00947-8

Lin Shi, Yichen Xu, Shiying Fan, Zixiao Yin, Guofan Qin, Jianguo Zhang, Anchao Yang

引用次数: 0

Smartphone-derived multidomain features including voice, finger-tapping movement and gait aid early identification of Parkinson’s disease 智能手机衍生的多领域特征，包括语音、手指敲击运动和步态，有助于帕金森病的早期识别

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-05 DOI: 10.1038/s41531-025-00953-w

Wee-Shin Lim, Sung-Pin Fan, Shu-I Chiu, Meng-Ciao Wu, Pu-He Wang, Kun-Pei Lin, Yung-Ming Chen, Pei-Ling Peng, Jyh-Shing Roger Jang, Chin-Hsien Lin

{"title":"Smartphone-derived multidomain features including voice, finger-tapping movement and gait aid early identification of Parkinson’s disease","authors":"Wee-Shin Lim, Sung-Pin Fan, Shu-I Chiu, Meng-Ciao Wu, Pu-He Wang, Kun-Pei Lin, Yung-Ming Chen, Pei-Ling Peng, Jyh-Shing Roger Jang, Chin-Hsien Lin","doi":"10.1038/s41531-025-00953-w","DOIUrl":"https://doi.org/10.1038/s41531-025-00953-w","url":null,"abstract":"Smart devices can easily capture changes in voice, movements, and gait in people with Parkinson’s disease (PD). We investigated whether smartphone-derived multimodal features combined with machine learning algorithms can aid in early PD identification. We recruited 496 participants, split into a training cohort (127 PD patients during “on” phase and 198 age-matched controls) and a test dataset (86 patients during “off” phase and 85 age-matched controls). Multidomain features from smartphone recordings were analyzed using machine learning classifiers with integration of a hyperparameter grid. Single-modality models for voice, hand movements, and gait showed diagnostic values of 0.88, 0.74, and 0.81, respectively, with test dataset values of 0.80, 0.74, and 0.76. An integrated multimodal model using a support vector machine improved performance to 0.86 and achieved 0.82 for identifying early-stage PD during the “off” phase. A smartphone-based integrated multimodality model combining voice, hand movement, and gait shows promise for early PD identification.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"12 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909705","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

Differences in age-related distribution of CSF alpha-synuclein seeding and Alzheimer profiles between PD with and without GBA1 variants 伴有和不伴有GBA1变异的PD之间CSF α -突触核蛋白种子的年龄相关分布和阿尔茨海默病谱的差异

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-05 DOI: 10.1038/s41531-025-00978-1

Stefanie Lerche, Isabel Wurster, Benjamin Roeben, Milan Zimmermann, Marcello Rossi, Angela Mammana, Simone Baiardi, Ann‑Kathrin Hauser, Christian Deuschle, Claudia Schulte, Piero Parchi, Kathrin Brockmann

引用次数: 0

Emergent glutamate & dopamine dysfunction in VPS35(D620N) knock-in mice and rapid reversal by LRRK2 inhibition VPS35（D620N）敲入小鼠出现谷氨酸和多巴胺功能障碍及LRRK2抑制的快速逆转

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-03 DOI: 10.1038/s41531-025-00948-7

A. Kamesh, C. A. Kadgien, N. Kuhlmann, S. Coady, A. Pietrantonio, Y. Cousineau, A. Khayachi, A. Jurado Santos, E. P. Hurley, J. C. Barron, M. P. Parsons, A. J. Milnerwood

{"title":"Emergent glutamate & dopamine dysfunction in VPS35(D620N) knock-in mice and rapid reversal by LRRK2 inhibition","authors":"A. Kamesh, C. A. Kadgien, N. Kuhlmann, S. Coady, A. Pietrantonio, Y. Cousineau, A. Khayachi, A. Jurado Santos, E. P. Hurley, J. C. Barron, M. P. Parsons, A. J. Milnerwood","doi":"10.1038/s41531-025-00948-7","DOIUrl":"https://doi.org/10.1038/s41531-025-00948-7","url":null,"abstract":"The D620N variant in Vacuolar Protein Sorting 35 (VPS35) causes autosomal-dominant, late-onset Parkinson’s disease. VPS35 is a core subunit of the retromer complex that canonically recycles transmembrane cargo from sorting endosomes. Although retromer cargoes include many synaptic proteins, VPS35’s neuronal functions are poorly understood. To investigate the consequences of the Parkinson’s mutation, striatal neurotransmission was assessed in 1- to 6-month-old VPS35 D620N knock-in (VKI) mice. Spontaneous and optogenetically-evoked corticostriatal glutamate transmission was increased in VKI spiny projection neurons by 6 months and was unaffected by acute leucine-rich repeat kinase 2 (LRRK2) inhibition. Total striatal glutamate release by iGluSnFR imaging was similar to wild-type. dLight imaging revealed robust increases in VKI striatal dopamine release by 6 months, which were reversed with acute LRRK2 kinase inhibition. We conclude that increased striatal neurotransmission in VKI mice progressively emerges in young-adulthood, and that dopamine dysfunction is likely the result of sustained, rapidly-reversible, LRRK2 hyperactivity.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"58 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903121","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

Automatic speech analysis combined with machine learning reliably predicts the motor state in people with Parkinson’s disease 结合机器学习的自动语音分析可以可靠地预测帕金森病患者的运动状态

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-05-02 DOI: 10.1038/s41531-025-00959-4

Tabea Thies, Elisa Mallick, Johannes Tröger, Ebru Baykara, Doris Mücke, Michael T. Barbe

{"title":"Automatic speech analysis combined with machine learning reliably predicts the motor state in people with Parkinson’s disease","authors":"Tabea Thies, Elisa Mallick, Johannes Tröger, Ebru Baykara, Doris Mücke, Michael T. Barbe","doi":"10.1038/s41531-025-00959-4","DOIUrl":"https://doi.org/10.1038/s41531-025-00959-4","url":null,"abstract":"It is still under debate whether levodopa treatment improves speech functions in Parkinson’s disease (PD). Therefore, speech functions of people with PD were compared in medication-OFF condition (withdrawal of PD medication for at least 12 h) and medication-ON condition (after receiving 200 mg of soluble levodopa). A total of 78 participants, including 51 males and 27 females, performed predefined standard speech tasks. Acoustic speech features were automatically extracted with the algorithm given by the Dysarthria Analyzer. Results suggest that acute levodopa intake improves phonatory-respiratory speech functions and speech planning abilities, while the articulatory system remains unaffected. Furthermore, the study provided preliminary evidence that speech function is able to predict the medication status in individuals with PD as the constructed speech-based biomarker score did not only correlate with established measures of (speech) motor impairment but could also differentiate between the medication OFF and ON status. A post-hoc machine learning model yielded similar results.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"8 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901268","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 diagnostic pathway of Parkinson’s disease: understanding patient perspectives in Australia 帕金森病的诊断途径：了解澳大利亚患者的观点

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-04-30 DOI: 10.1038/s41531-025-00968-3

Tali Lang, Iain McLean, Jenna Shin, Victoria Jackson, Isobel Lawrenson, Belinda Zipper, Alex Yeung, Andrew Evans, Grant Dewson

{"title":"The diagnostic pathway of Parkinson’s disease: understanding patient perspectives in Australia","authors":"Tali Lang, Iain McLean, Jenna Shin, Victoria Jackson, Isobel Lawrenson, Belinda Zipper, Alex Yeung, Andrew Evans, Grant Dewson","doi":"10.1038/s41531-025-00968-3","DOIUrl":"https://doi.org/10.1038/s41531-025-00968-3","url":null,"abstract":"There is limited data about experiences of people with Parkinson’s (PwP) in Australia. This study, initiated and co-designed by PwP, surveyed 385 participants nationally (335 fully completed the questionnaire). Participants living in capital and regional city centers reported satisfaction with clinical care during diagnostic consultation at approximately 40%, with satisfaction less in rural areas (26%). 68% of participants reported inadequate involvement in discussions about treatment and care planning and 77% were dissatisfied with the support following diagnosis. Respondents reported low referral rates to allied health services such as physiotherapy (22%) and mental health services (17%). Feedback indicated support could improved by increased access to Parkinson’s disease Clinical Nurse Specialists and to educational resources and support. Findings highlight the need to establish Australian guidelines for Parkinson’s clinical management, greater resourcing for clinicians including development of educational programs, and creation of Australian-centric educational resources to improve quality of care for PwP.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"20 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893125","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