NPJ Parkinson's Disease最新文献

Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-11 DOI: 10.1038/s41531-025-00899-z

Justin Moore, Timothy Wu, Justin Dhindsa, Omar El Fadel, Anh Le, Alma Perez, Bismark Amoh, Akash Tarkunde, Katy F. Zhu, Matthew Avalos, Eric B. Dammer, Duc M. Duong, Nicholas T. Seyfried, Joshua M. Shulman, Ismael Al-Ramahi, Juan Botas

{"title":"Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson’s disease","authors":"Justin Moore, Timothy Wu, Justin Dhindsa, Omar El Fadel, Anh Le, Alma Perez, Bismark Amoh, Akash Tarkunde, Katy F. Zhu, Matthew Avalos, Eric B. Dammer, Duc M. Duong, Nicholas T. Seyfried, Joshua M. Shulman, Ismael Al-Ramahi, Juan Botas","doi":"10.1038/s41531-025-00899-z","DOIUrl":"https://doi.org/10.1038/s41531-025-00899-z","url":null,"abstract":"Parkinson’s disease (PD) starts decades before symptoms appear, usually in the later decades of life, when age-related changes are occurring. To identify molecular changes early in the disease course and distinguish PD pathologies from aging, we generated Drosophila expressing alpha-synuclein (αSyn) in neurons and performed longitudinal bulk transcriptomics and proteomics on brains at six time points across the lifespan and compared the data to healthy control flies as well as human post-mortem brain datasets. We found that translational and energy metabolism pathways were downregulated in αSyn flies at the earliest timepoints; comparison with the aged control flies suggests that elevated αSyn accelerates changes associated with normal aging. Unexpectedly, single-cell analysis at a mid-disease stage revealed that neurons upregulate protein synthesis and nonsense-mediated decay, while glia drive their overall downregulation. Longitudinal multi-omics approaches in animal models can thus help elucidate the molecular cascades underlying neurodegeneration vs. aging and co-pathologies.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"66 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599357","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

Race and ethnicity matter! Moving Parkinson’s risk research towards diversity and inclusiveness

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-07 DOI: 10.1038/s41531-025-00891-7

Sara Siddiqi, Zoe Ortiz, Stephanie Simard, Juan Li, Kamaya Lawrence, Melissa Redmond, Julianna J. Tomlinson, Michael G. Schlossmacher, Natalina Salmaso

引用次数: 0

SVHRSP protects against rotenone-induced neurodegeneration in mice by inhibiting TLR4/NF-κB-mediated neuroinflammation via gut microbiota

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-06 DOI: 10.1038/s41531-025-00892-6

Mengdi Chen, Yu Zhang, Liyan Hou, Zirui Zhao, Peiyan Tang, Qingquan Sun, Jie Zhao, Qingshan Wang

{"title":"SVHRSP protects against rotenone-induced neurodegeneration in mice by inhibiting TLR4/NF-κB-mediated neuroinflammation via gut microbiota","authors":"Mengdi Chen, Yu Zhang, Liyan Hou, Zirui Zhao, Peiyan Tang, Qingquan Sun, Jie Zhao, Qingshan Wang","doi":"10.1038/s41531-025-00892-6","DOIUrl":"https://doi.org/10.1038/s41531-025-00892-6","url":null,"abstract":"Strong evidence indicates that remodeling gut microbiota may be an effective approach to combat Parkinson’s disease (PD). Scorpion Venom Heat-Resistant Synthesized Peptide (SVHRSP), a synthesized peptide discovered from scorpion venom, displays potent neuroprotection in multiple PD models. However, the potential mechanisms remain unclear. In this study, we demonstrated that SVHRSP effectively attenuated gastrointestinal function impairments and reinstated the microbiota composition in rotenone-induced PD mouse model. Microbiota depletion and FMT verified that the restored gut microbiota was necessary for SVHRSP-mediated neuroprotection against dopaminergic neurodegeneration in rotenone PD mice. Furthermore, SVHRSP gut microbiota-dependently attenuated BBB impairment, microglial activation, and gene expression of pro-inflammatory factors in rotenone-treated mice. Mechanistically, SVHRSP decreased the concentrations of LPS and HMGB1 in both serum and brain tissue, thereby inhibiting the TLR4/NF-κB signaling pathway in the brain of rotenone-treated mice. Together, our findings provided fresh perspectives on the mechanisms underlying SVHRSP-induced neuroprotection in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"53 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560929","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

Atrophy of ventral diencephalon is associated with freezing of gait in Parkinson’s disease: analysis of two cohorts

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-06 DOI: 10.1038/s41531-025-00893-5

Xuemei Wang, Huimin Chen, Xinxin Ma, Huijing Liu, Dongdong Wu, Wei Du, Jing He, Shuhua Li, Haibo Chen, Tao Wu, Tao Feng, Wen Su

引用次数: 0

A personalised and comprehensive approach is required to suppress or replenish SNCA for Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-04 DOI: 10.1038/s41531-025-00887-3

Dunhui Li, Wai Yan Yau, Shengdi Chen, Steve Wilton, Frank Mastaglia

引用次数: 0

Male sex accelerates cognitive decline in GBA1 Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-04 DOI: 10.1038/s41531-025-00883-7

Silvia Paola Caminiti, Micol Avenali, Alice Galli, Rachele Malito, Giada Cuconato, Caterina Galandra, Rosaria Calabrese, Andrea Pilotto, Alessandro Padovani, Fabio Blandini, Daniela Perani, Cristina Tassorelli, Enza Maria Valente

{"title":"Male sex accelerates cognitive decline in GBA1 Parkinson’s disease","authors":"Silvia Paola Caminiti, Micol Avenali, Alice Galli, Rachele Malito, Giada Cuconato, Caterina Galandra, Rosaria Calabrese, Andrea Pilotto, Alessandro Padovani, Fabio Blandini, Daniela Perani, Cristina Tassorelli, Enza Maria Valente","doi":"10.1038/s41531-025-00883-7","DOIUrl":"https://doi.org/10.1038/s41531-025-00883-7","url":null,"abstract":"We evaluated 128 GBA and 432 nonGBA Parkinson’s disease (PD) subjects available from Parkinson’s Progression Markers Initiative. Baseline clinical features and dopaminergic activity were assessed, together with clinical follow-up (6.87 ± 3.2 years). Survival analyses assessed the independent and interactive effects of sex and GBA1 mutations on cognitive decline. At baseline, GBA-PD males showed severe motor impairment, sleep disorders and memory deficits. Despite milder motor deficit, compared to GBA-PD males, GBA-PD females showed greater dopaminergic denervation, suggesting the effect of neural reserve. In longitudinal assessment, GBA-PD males showed greater MoCA rate of change per year and greater risk of cognitive impairment than GBA-PD females and nonGBA-PD. In GBA-PD males, both late age at onset and “severe/mild” GBA variants were associated with increased risk of cognitive impairment. Male sex and GBA1 carrier status have an additive value in increasing the risk of cognitive decline in PD. The effect of sex on GBA1-related pathology warrants further examination to address future trials design and patients’ selection.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"17 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538438","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

Author Correction: A framework for translational therapy development in deep brain stimulation.

IF 6.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-04 DOI: 10.1038/s41531-025-00890-8

Jiazhi Chen, Jens Volkmann, Chi Wang Ip

引用次数: 0

Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson’s disease: A DNA co-methylation network analysis

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-02 DOI: 10.1038/s41531-025-00877-5

Joshua Harvey, Adam R. Smith, Luke S. Weymouth, Rebecca G. Smith, Isabel Castanho, Leon Hubbard, Byron Creese, Catherine Bresner, Nigel Williams, Ehsan Pishva, Katie Lunnon

引用次数: 0

Z/Ce@hemin enzymes with enhanced peroxidase activity for monitoring and screening the oxidative stress models of Parkinson’s disease

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-01 DOI: 10.1038/s41531-025-00875-7

Li Lei, Xiuli Chen, Xincheng Long, Qiuxia Tu, Liping Zhao, Dan Huang, Lingli Song, Jiaojiao Wang, Suzhen Zhai, Xiaozhong Chen, Chunlin Zhang

{"title":"Z/Ce@hemin enzymes with enhanced peroxidase activity for monitoring and screening the oxidative stress models of Parkinson’s disease","authors":"Li Lei, Xiuli Chen, Xincheng Long, Qiuxia Tu, Liping Zhao, Dan Huang, Lingli Song, Jiaojiao Wang, Suzhen Zhai, Xiaozhong Chen, Chunlin Zhang","doi":"10.1038/s41531-025-00875-7","DOIUrl":"https://doi.org/10.1038/s41531-025-00875-7","url":null,"abstract":"Inspired by natural enzymes, artificial enzymes have garnered significant interest due to their simplicity of production, robustness under harsh conditions, and enhanced stability. This study introduces, for the first time, a novel Z/Ce@hemin composite enzyme, constructed by anchoring hemin onto zeolitic imidazolate framework-8 (ZIF-8)-encapsulated ceria (CeO2) nanoparticles. This innovative design overcomes the challenges of hemin dimerization, enhances substrate affinity, and accelerates mass transport, leading to significantly improved peroxidase-like activity. The enzyme also demonstrates remarkable stability and resistance to environmental interference. Utilizing this Z/Ce@hemin composite, a sensitive and selective colorimetric detection system was developed for rapid and accurate quantification of hydrogen peroxide (H2O2), a key oxidative stress marker. This approach was successfully applied in cellular models and Caenorhabditis elegans models of Parkinson’s disease, enabling precise monitoring of H2O2. The study provides a groundbreaking platform for oxidative stress modeling and expands possibilities in neurodegenerative disease research and therapeutic screening.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"51 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526181","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

Transcutaneous auricular vagus nerve stimulation improves cortical functional topological properties and intracortical facilitation in patients with Parkinson’s disease 经皮耳廓迷走神经刺激可改善帕金森病患者的皮层功能拓扑特性和皮层内促进作用

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-01 DOI: 10.1038/s41531-025-00889-1

Heng Zhang, Ai-di Shan, Ya-yi Huang, Meng-xi Gao, Chen-hui Wan, Shi-yi Ye, Cai-ting Gan, Hui-min Sun, Xing-yue Cao, Yong-sheng Yuan, Ke-zhong Zhang

{"title":"Transcutaneous auricular vagus nerve stimulation improves cortical functional topological properties and intracortical facilitation in patients with Parkinson’s disease","authors":"Heng Zhang, Ai-di Shan, Ya-yi Huang, Meng-xi Gao, Chen-hui Wan, Shi-yi Ye, Cai-ting Gan, Hui-min Sun, Xing-yue Cao, Yong-sheng Yuan, Ke-zhong Zhang","doi":"10.1038/s41531-025-00889-1","DOIUrl":"https://doi.org/10.1038/s41531-025-00889-1","url":null,"abstract":"Our study aimed to investigate the neural mechanisms of taVNS in the motor symptoms of PD, focusing on the topological properties of cortical functional networks and cortical excitability. Thirty-two PD patients underwent functional near‐infrared spectroscopy and transcranial magnetic stimulation evaluation prior to and after two-week taVNS, which were controlled by 20 healthy controls (HCs). PD patients exhibited decreased nodal efficiency (Ne) in the right M1 and increased Ne in the left pre‐motor and supplementary motor area compared with HCs. The decreased Ne in the right M1 was negatively associated with UPDRS-III scores. Interestingly, taVNS treatment improved PD motor symptoms by increasing Ne in the right M1 and enhancing intracortical facilitation (ICF, ISI 10, and 15 ms). The increased Ne and ICF (ISI 15 ms) were negatively correlated with the decreased UPDRS-III scores. taVNS could improve nodal information processing efficiency in the M1 and enhance cortical facilitation to improve PD motor disorders.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"1 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528270","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