NPJ Parkinson's Disease最新文献

The biological clock in parkinson's disease: mechanisms and chronotherapy. 帕金森病的生物钟：机制和时间疗法。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2026-05-09 DOI: 10.1038/s41531-026-01379-8

Hong Liu, Hao Ling, Kangchao Sun, Kun Yang, Wenzhen Du, Yuxiu Ma, Yaru Wang, Kai Wang, Ying Liu, Long Niu

引用次数: 0

Identifying maximal beta power from directional subthalamic local field potentials in Parkinson's disease. 从帕金森病的定向丘脑下局部场电位确定最大β功率。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2026-05-08 DOI: 10.1038/s41531-026-01380-1

Jennifer K Behnke, Robert L Peach, Moritz Gerster, Richard M Köhler, Jeroen G V Habets, Johannes L Busch, Varvara Mathiopoulou, Jonathan Kaplan, Lucia K Feldmann, Juliette Vivien, Chi Wang Ip, Gerd-Helge Schneider, Katharina Faust, Patricia Krause, Andrea A Kühn

引用次数: 0

High molecular weight insoluble parkin in the substantia nigra of patients with idiopathic Parkinson's disease. 特发性帕金森病患者黑质中的高分子量不溶性帕金森。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2026-05-07 DOI: 10.1038/s41531-026-01371-2

Cyntia Tremblay, Laura Pshevorskiy, Rosalie J Cottez, Hélèna L Denis, Vincent Emond, Marc Morissette, Ali H Rajput, Thérèse Di Paolo, Alex Rajput, Frédéric Calon

{"title":"High molecular weight insoluble parkin in the substantia nigra of patients with idiopathic Parkinson's disease.","authors":"Cyntia Tremblay, Laura Pshevorskiy, Rosalie J Cottez, Hélèna L Denis, Vincent Emond, Marc Morissette, Ali H Rajput, Thérèse Di Paolo, Alex Rajput, Frédéric Calon","doi":"10.1038/s41531-026-01371-2","DOIUrl":"https://doi.org/10.1038/s41531-026-01371-2","url":null,"abstract":"Parkinson's disease (PD) is characterized by a loss of dopaminergic neurons and accumulation of α-synuclein (α-syn)-containing Lewy bodies in the substantia nigra (SN) pars compacta. Mutations in the gene coding for the protein parkin cause a form of autosomal recessive juvenile parkinsonism, but its role in idiopathic PD is poorly understood. Here, to investigate parkin changes in the SN in PD, we established a clinicopathology research platform comparing PD patients (n = 24) with Controls (n = 21). We first confirmed the massive loss of dopamine (DA) levels (-96%) in the putamen of PD patients, using HPLC/electrochemistry. Higher levels of phosphorylated α-syn (αsynP129) (23-fold) were observed in the SN of PD patients by Western immunoblotting. In formic acid extracts, an increase in the insoluble oligomeric form of parkin migrating at 260 kDa was observed (+ 49%) in the SN of PD patients, along with lower levels of the 55 kDa monomeric form (-47%). These changes in parkin were specific for the SN, and not observed in the putamen, parietal cortex and cerebellum. High molecular weight parkin correlated with αsynP129 levels and dopamine loss and was more prominently found in PD patients with levodopa-induced dyskinesias. Additional studies in animal models suggest that the aggregation of parkin is not a direct consequence of dopaminergic depletion or αsyn overproduction, but a component of PD cellular pathophysiology. Taken together, the results reported herein show that, beside dopamine loss and increased αsynP129, neurodegeneration in idiopathic PD is associated with a conversion of parkin into an insoluble high molecular weight form in the SN.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841296","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

Shared gene signatures and biochemical regulatory networks linking Parkinson's disease and ulcerative colitis. 帕金森病和溃疡性结肠炎的共享基因特征和生化调控网络。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2026-05-06 DOI: 10.1038/s41531-026-01374-z

Xiaohui Sun, Zhichen An, Shufei Wang, Kongjia Wang

{"title":"Shared gene signatures and biochemical regulatory networks linking Parkinson's disease and ulcerative colitis.","authors":"Xiaohui Sun, Zhichen An, Shufei Wang, Kongjia Wang","doi":"10.1038/s41531-026-01374-z","DOIUrl":"10.1038/s41531-026-01374-z","url":null,"abstract":"Epidemiological studies suggest an association between Parkinson's disease (PD) and ulcerative colitis (UC), yet the molecular programs potentially linking these disorders remain poorly defined. Here, we integrated curated disease-gene resources with publicly available blood transcriptomic datasets to identify shared molecular features across PD and UC. We identified 320 shared signature genes and a topology-derived 10-gene core module that included TNF, IL1B, TP53, BCL2, and CASP3. Enrichment analyses implicated a convergent inflammatory-stress architecture characterized by microbial-response, oxidative-stress, lipid/inflammatory, and IL-17-related signaling programs. Immune deconvolution revealed partially overlapping peripheral immune alterations in PD and UC, most notably reduced memory B-cell abundance. Network analyses further highlighted TP53 and JUN as major transcriptional hubs and prioritized several candidate compounds for follow-up investigation. Cross-validation and external validation showed that only a subset of the core genes retained stable discriminatory performance across cohorts, indicating that network centrality did not uniformly translate into robust classifier-like behavior. Collectively, these findings support a shared inflammatory/apoptotic regulatory module linking PD and UC and provide a systems-level framework for mechanistic studies and therapeutic prioritization, rather than a definitive biomarker panel.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"12 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The epitranscriptomic m6A RNA modification modulates the synapse in ageing and in a mouse model of synucleinopathy. 外转录组m6A RNA修饰在衰老和突触核蛋白病小鼠模型中调节突触。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2026-05-06 DOI: 10.1038/s41531-026-01362-3

Avika Chopra, Mary Xylaki, Fanzheng Yin, Ricardo Castro-Hernández, Madiha Merghani, Valentina Grande, Brit Mollenhauer, André Fischer, Tiago F Outeiro

{"title":"The epitranscriptomic m6A RNA modification modulates the synapse in ageing and in a mouse model of synucleinopathy.","authors":"Avika Chopra, Mary Xylaki, Fanzheng Yin, Ricardo Castro-Hernández, Madiha Merghani, Valentina Grande, Brit Mollenhauer, André Fischer, Tiago F Outeiro","doi":"10.1038/s41531-026-01362-3","DOIUrl":"https://doi.org/10.1038/s41531-026-01362-3","url":null,"abstract":"N6-methyladenosine (m6A) is the most abundant transcriptional modification in eukaryotic RNA, regulating RNA fate. While the functions of m6A in the development of the mammalian brain have been extensively studied, its role in synaptic plasticity, and brain function remain underexplored. The involvement of this modification in Parkinson's disease and other synucleinopathies has only recently been studied, and needs further investigation. Here, we investigated the m6A epitranscriptome using MeRIP-seq in A30P-aSyn transgenic mice (aSyn Tg). We observed hypermethylation of synaptic genes in young aSyn Tg mice compared to age-matched control mice. The methylation was reduced during ageing. Using immunofluorescence imaging and biochemical analysis, we further investigated the levels and distribution of m6A regulatory enzymes-writer, METTL3, reader, YTHDF1, and eraser, FTO, in the cortex, striatum, hippocampus, and cerebellum of aSyn Tg and control mice, and in primary cortical neuronal cultures. While the levels of these proteins were similar, METTL3 was found in the nucleus and in the post-synaptic compartment in neurons, suggesting it may play a role in methylation at the post-synapse. Our findings suggest that alterations in the regulation of m6A RNA methylation may be associated with neurodegeneration and ageing and it may play a significant role at the synapse.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841325","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

Allergic disease as a risk factor for Parkinson's disease: a possible role of eosinophil. 过敏性疾病作为帕金森病的危险因素：嗜酸性粒细胞的可能作用。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2026-05-06 DOI: 10.1038/s41531-026-01377-w

Hee Jin Chang, Su Hyeon Ha, So-Hee Lee, Seungmin Lee, Chanhee Jeong, Jung Hwan Shin, Han-Joon Kim, Heung-Woo Park

{"title":"Allergic disease as a risk factor for Parkinson's disease: a possible role of eosinophil.","authors":"Hee Jin Chang, Su Hyeon Ha, So-Hee Lee, Seungmin Lee, Chanhee Jeong, Jung Hwan Shin, Han-Joon Kim, Heung-Woo Park","doi":"10.1038/s41531-026-01377-w","DOIUrl":"https://doi.org/10.1038/s41531-026-01377-w","url":null,"abstract":"Neuroinflammation is central to Parkinson's disease (PD) pathogenesis and allergic inflammation may contribute to PD risk, but evidence is limited. Using the Korean National Health Insurance Service database, we conducted a cohort study of 5,036,518 adults aged ≥40 years who underwent health examination in 2009 and identified incident PD from 2010 to 2019, excluding prior PD. Asthma, allergic rhinitis, and atopic dermatitis were defined by ICD-10 codes and healthcare utilization, and severity by annual outpatient visits. Cox proportional hazards models estimated hazard ratios (HRs) adjusting for demographics, lifestyle, and comorbidities. We compared eosinophil and neutrophil counts between 234 hospital-based PD patients and 468 controls. During follow-up, 44,621 PD cases occurred (0.9/1000 person-years). PD incidence was increased in asthma (HR 1.16; 95% CI 1.07-1.24) and allergic rhinitis (HR 1.18; 95% CI 1.14-1.22), but not atopic dermatitis. Risk increased with multiple allergic conditions (ptrend <0.001) and higher visit frequency (≥3/year: HR 1.26; 95% CI 1.16-1.38). In the hospital cohort, PD patients showed higher eosinophil and neutrophil counts, elevated eosinophil/neutrophil ratio, and more frequent eosinophilia ≥200 cells/µL (all p < 0.05). Asthma and allergic rhinitis were associated with increased PD incidence, particularly with greater severity and multimorbidity, supporting shared inflammatory mechanisms.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841283","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

Individual cases of Parkinson's disease can be robustly classified using magnetoencephalography. 帕金森氏病的个体病例可以使用脑磁图进行可靠的分类。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2026-05-06 DOI: 10.1038/s41531-026-01345-4

Gillian Roberts, Samuel Hardy, Yali Pan, Robert Chen, Benjamin T Dunkley

{"title":"Individual cases of Parkinson's disease can be robustly classified using magnetoencephalography.","authors":"Gillian Roberts, Samuel Hardy, Yali Pan, Robert Chen, Benjamin T Dunkley","doi":"10.1038/s41531-026-01345-4","DOIUrl":"https://doi.org/10.1038/s41531-026-01345-4","url":null,"abstract":"Parkinson's disease (PD) is a progressive neurodegenerative disorder that causes debilitating symptoms in both the motor and cognitive domains. The neurophysiological markers of PD include 'oscillopathies' such as diffuse neural oscillatory slowing, dysregulated beta band activity, and changes in interhemispheric functional connectivity; however, the relative importance of these markers as determinants of disease status is unclear. In this case-control study, we used resting state magnetoencephalography (MEG) data (n = 199 participants, 78 PD, 121 controls) from the OMEGA repository to investigate changes in spectral power and functional networks in PD. Using a Contrast of Parameter Estimates approach, we modelled the effects of PD while controlling for population-level confounds. Permutation testing revealed significant increases in theta (p = 0.0001) and decreases in gamma band spectral power (p = 0.0001). We also used a partial least squares-based classifier to find linear combinations of MEG features which independently predict PD. We found MEG-based predictions to be highly sensitive and specific, reaching an optimal AUC-ROC of 0.87 ± 0.04. Interpretation of the model indicates oscillatory slowing can be separated into components that can robustly identify individual cases of PD. This suggests MEG can reveal dissociable, complementary neural processes which contribute to PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841266","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

Matters arising: critical appraisal of device aided therapy outcomes in Parkinson's disease. 产生的问题：帕金森病设备辅助治疗结果的关键评估。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2026-05-06 DOI: 10.1038/s41531-026-01342-7

Qingliu Zheng, Changyun Liu

引用次数: 0

Hippocampal atrophy in untreated de novo Parkinson's disease with obstructive sleep apnea. 未经治疗的帕金森病伴阻塞性睡眠呼吸暂停患者的海马萎缩

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2026-05-05 DOI: 10.1038/s41531-026-01360-5

Kristína Burdová, Filip Růžička, Josef Mana, Pavel Filip, Jiří Nepožitek, Simona Dostálová, Pavla Peřinová, Ondrej Bezdicek, Petr Gregorovič, Filip Havlík, Evžen Růžička, Petr Dušek, Karel Šonka, Robert Jech

{"title":"Hippocampal atrophy in untreated de novo Parkinson's disease with obstructive sleep apnea.","authors":"Kristína Burdová, Filip Růžička, Josef Mana, Pavel Filip, Jiří Nepožitek, Simona Dostálová, Pavla Peřinová, Ondrej Bezdicek, Petr Gregorovič, Filip Havlík, Evžen Růžička, Petr Dušek, Karel Šonka, Robert Jech","doi":"10.1038/s41531-026-01360-5","DOIUrl":"https://doi.org/10.1038/s41531-026-01360-5","url":null,"abstract":"Over the course of Parkinson's disease (PD), there is considerable intersubject variability in gray matter (GM) loss across a wide range of subcortical structures and cortical areas, which is often predictive of the clinical trajectory of the disease. The biological or clinical factors underlying these individual differences are not well understood. Obstructive sleep apnea (OSA) is a sleep-disordered breathing that is associated with an increased risk of cognitive impairment and neurodegeneration. In this study, we investigated whether moderate-to-severe OSA in untreated de novo PD is linked to more severe GM atrophy compared to PD without OSA and a group of controls. High-resolution structural 3 T MRI T1 and T2-weighted scans were used to estimate subcortical GM volumes and hippocampal subfields, and to perform vertex-wise analyses of cortical thickness and cortical surface area. We found that the presence of OSA was associated with a significant bilateral reduction in hippocampal volume, particularly in the CA1, CA3, and subicular regions, an effect specifically observed in PD patients and not in the control group. These findings suggest that the co-occurrence of OSA and PD may be related to early structural brain changes, highlighting the importance of timely OSA diagnosis and management to potentially delay cognitive decline in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841269","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

Branched-chain amino acids ameliorate CD4⁺ T-cell-associated gut immune inflammation in Parkinson's disease. 支链氨基酸改善帕金森病CD4+ t细胞相关肠道免疫炎症。

IF 8.2 1区医学

NPJ Parkinson's Disease Pub Date : 2026-05-04 DOI: 10.1038/s41531-026-01375-y

Ke An, Danlei Wang, Yi Qu, Haoheng Yu, Hongming Liang, Zhijuan Mao, Zheng Xue, Jingyi Li

{"title":"Branched-chain amino acids ameliorate CD4+ T-cell-associated gut immune inflammation in Parkinson's disease.","authors":"Ke An, Danlei Wang, Yi Qu, Haoheng Yu, Hongming Liang, Zhijuan Mao, Zheng Xue, Jingyi Li","doi":"10.1038/s41531-026-01375-y","DOIUrl":"https://doi.org/10.1038/s41531-026-01375-y","url":null,"abstract":"Previous studies have shown that alterations in the gut microbiota and its derived metabolites, branched-chain amino acids (BCAAs), are correlated with T-cell-associated immune imbalance and Parkinson's disease (PD). However, the associations among BCAAs, gastrointestinal dysfunction and T-cell-related gut inflammation remain unclear. This study showed that the constipation symptoms in the PD mice persisted after chronic MPTP treatment. An imbalance in the CD4+ T-cell subtypes was observed in the colonic lamina propria (cLP), mesenteric lymph nodes (mLNs), and spleen. Metagenomic and metabolomic analyses showed that microbial dysbiosis promoted BCAA degradation rather than biosynthesis, and reduced BCAA levels were confirmed in the serum. BCAA supplementation alleviated constipation symptoms and increased Th1 and Th17 cell infiltration in the cLP, mLNs and spleen were significantly attenuated after BCAA treatment. This study highlights the therapeutic value of BCAAs in mitigating gut immune inflammation-associated constipation symptoms in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841322","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