NPJ Parkinson's Disease最新文献_第9页

Comparative analysis of Parkinson’s and inflammatory bowel disease gut microbiomes reveals shared butyrate-producing bacteria depletion 帕金森氏症和炎症性肠病肠道微生物组的比较分析揭示了共同的丁酸盐产生细菌枯竭

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-19 DOI: 10.1038/s41531-025-00894-4

Maeve E. Krueger, Jake Sondag Boles, Zachary D. Simon, Stephan D. Alvarez, Nikolaus R. McFarland, Michael S. Okun, Ellen M. Zimmermann, Christopher E. Forsmark, Malú Gámez Tansey

{"title":"Comparative analysis of Parkinson’s and inflammatory bowel disease gut microbiomes reveals shared butyrate-producing bacteria depletion","authors":"Maeve E. Krueger, Jake Sondag Boles, Zachary D. Simon, Stephan D. Alvarez, Nikolaus R. McFarland, Michael S. Okun, Ellen M. Zimmermann, Christopher E. Forsmark, Malú Gámez Tansey","doi":"10.1038/s41531-025-00894-4","DOIUrl":"https://doi.org/10.1038/s41531-025-00894-4","url":null,"abstract":"Epidemiological studies reveal that inflammatory bowel disease (IBD) is associated with an increased risk of Parkinson’s disease (PD). Gut dysbiosis has been documented in both PD and IBD, however it is currently unknown whether gut dysbiosis underlies the epidemiological association between both diseases. To identify shared and distinct features of the PD and IBD microbiome, we recruited 54 PD, 26 IBD, and 16 healthy control individuals and performed the first joint analysis of gut metagenomes. Larger, publicly available PD and IBD metagenomic datasets were also analyzed to validate and extend our findings. Depletions in short-chain fatty acid (SCFA)-producing bacteria, including Roseburia intestinalis, Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium rectale, as well depletion in SCFA-synthesis pathways were detected across PD and IBD datasets, suggesting that depletion of these microbes in IBD may influence the risk for PD development.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"109 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661371","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 Enterococcus faecalis and tyrosine decarboxylase gene levels with levodopa pharmacokinetics in Parkinson’s disease 粪肠球菌和酪氨酸脱羧酶基因水平与帕金森病患者左旋多巴药代动力学的关系

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-18 DOI: 10.1038/s41531-025-00903-6

Noriyuki Miyaue, Haruto Yamamoto, Shuang Liu, Yuko Ito, Yuki Yamanishi, Rina Ando, Yasuyuki Suzuki, Masaki Mogi, Masahiro Nagai

{"title":"Association of Enterococcus faecalis and tyrosine decarboxylase gene levels with levodopa pharmacokinetics in Parkinson’s disease","authors":"Noriyuki Miyaue, Haruto Yamamoto, Shuang Liu, Yuko Ito, Yuki Yamanishi, Rina Ando, Yasuyuki Suzuki, Masaki Mogi, Masahiro Nagai","doi":"10.1038/s41531-025-00903-6","DOIUrl":"https://doi.org/10.1038/s41531-025-00903-6","url":null,"abstract":"Multiple factors affect the absorption of orally administered levodopa, the gold standard for the treatment of Parkinson’s disease (PD). Enterococcus faecalis (E. faecalis) expresses the enzyme tyrosine decarboxylase (tyrDC), which metabolizes levodopa into dopamine and thereby may influence its absorption in patients with PD. This study investigated the association between fecal E. faecalis and tyrDC gene levels and the pharmacokinetics of orally administered levodopa in 21 patients with PD. Our results revealed a significant association between elevated fecal levels of E. faecalis and tyrDC gene levels and reduced peak plasma levodopa concentrations. Additionally, among patients receiving levodopa-carbidopa intestinal gel treatment, strong positive correlations were observed between E. faecalis and tyrDC gene levels in fecal samples and those from the tip of the jejunal tube. Further prospective studies are required to explore the potential role of gut microbiota as a therapeutic target in patients with PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"33 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641051","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

A PheWAS approach to identify associations of GBA1 variants with comprehensive phenotypes beyond neurological diseases PheWAS方法鉴定GBA1变异与神经系统疾病以外的综合表型的关联

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-17 DOI: 10.1038/s41531-025-00901-8

Jiaqi Yang, Yuanfeng Huang, Zheng Wang, Shiyu Zhang, Dai Wu, Jiayi Xiong, Heng Wu, Yijing Wang, Qiao Zhou, Yixiao Zhu, Guihu Zhao, Bin Li, Jifeng Guo, Kun Xia, Beisha Tang, Jinchen Li

{"title":"A PheWAS approach to identify associations of GBA1 variants with comprehensive phenotypes beyond neurological diseases","authors":"Jiaqi Yang, Yuanfeng Huang, Zheng Wang, Shiyu Zhang, Dai Wu, Jiayi Xiong, Heng Wu, Yijing Wang, Qiao Zhou, Yixiao Zhu, Guihu Zhao, Bin Li, Jifeng Guo, Kun Xia, Beisha Tang, Jinchen Li","doi":"10.1038/s41531-025-00901-8","DOIUrl":"https://doi.org/10.1038/s41531-025-00901-8","url":null,"abstract":"Given the established association between numerous GBA1 variants and specific neurological diseases, we extended the exploration by a phenome-wide association study to assess the impact of GBA1 variants on a wider spectrum of health-related traits. We identified 41 phenotypes associated with GBA1 variants, 39 of which were unreported, including 21 non-neurological and 20 neurological phenotypes. Based on variant-level association tests, we found beyond the neurological phenotypes particularly decreased gray-white matter contrast measures across 13 distinct brain regions, the non-coding variant rs9628662 was associated with six non-neurological traits such as hypermetropia. Another non-coding variant rs3115534 showed associations with eight biomarkers of multiple categories, and an increased risk of benign digestive neoplasms. Notably, compared to protein-coding variant p.T408M, the rs3115534 had opposing effects on three hematological biomarkers. Additionally, gene-level association analyses revealed significant associations with three neurological diseases including Parkinson’s disease. The findings demonstrated that GBA1 variants significantly impact various health-related traits.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"61 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641058","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

Lysophosphatidylcholine promoting α-Synuclein aggregation in Parkinson’s disease: disrupting GCase glycosylation and lysosomal α-Synuclein degradation 溶血磷脂酰胆碱促进帕金森病中α-突触核蛋白的聚集：干扰 GCase 糖基化和溶酶体中α-突触核蛋白的降解

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-03-15 DOI: 10.1038/s41531-025-00902-7

Chunyan Mu, Kaiquan Shao, Mingyu Su, Yurong Guo, Yuxiang Qiu, Ruiao Sun, Sihan Sun, Yaoyu Sun, Chenkai Liu, Wei Wang, Xiaoling Qin, Chuanxi Tang

{"title":"Lysophosphatidylcholine promoting α-Synuclein aggregation in Parkinson’s disease: disrupting GCase glycosylation and lysosomal α-Synuclein degradation","authors":"Chunyan Mu, Kaiquan Shao, Mingyu Su, Yurong Guo, Yuxiang Qiu, Ruiao Sun, Sihan Sun, Yaoyu Sun, Chenkai Liu, Wei Wang, Xiaoling Qin, Chuanxi Tang","doi":"10.1038/s41531-025-00902-7","DOIUrl":"https://doi.org/10.1038/s41531-025-00902-7","url":null,"abstract":"In Parkinson’s Disease (PD), elevated serum lysophosphatidylcholine (LPC) levels correlate with disease progression. However, the mechanisms by which abnormal LPC elevation contributes to PD-related neurotoxicity remain poorly understood. This study aims to investigate the pathogenic role of LPC in dopaminergic neuronal damage and elucidates its underlying mechanisms. Our results showed LPC induces α-synuclein aggregation, exacerbating cognitive dysfunction. LPC activates Cleaved-Caspase3 via the orphan receptor GPR35-ERK signaling pathway, inhibits GRASP65 expression, and disrupts the polarized structure of the Golgi apparatus. This disruption impairs glycosylation and function of glucocerebrosidase (GCase), preventing its transport to lysosomes and leading to glucosylceramide (GlcCer) accumulation, a scaffold for α-synuclein aggregation. LPC also disrupts the autophagolysosomal pathway and lysosomal acidification, exacerbating toxic α-synuclein accumulation. Restoring GCase glycosylation, limiting GlcCer synthesis, or blocking ERK signaling mitigates these effects. This study highlights LPC’s role in promoting α-synuclein aggregation and autophagolysosomal dysfunction, advancing our understanding of PD pathology.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"18 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631380","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

Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson’s disease 纵向多组学在α -突触核蛋白果蝇模型中区分帕金森病与年龄相关的病理

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 种族和民族很重要！推动帕金森氏症风险研究走向多元化和包容性

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 SVHRSP通过肠道菌群抑制TLR4/NF-κ b介导的神经炎症，对鱼藤酮诱导的小鼠神经退行性变具有保护作用

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 帕金森病患者腹侧间脑萎缩与步态冻结有关：两组队列分析

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 需要一种个性化和全面的方法来抑制或补充帕金森病的SNCA

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 男性性行为加速GBA1帕金森病的认知能力下降

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