Molecular Neurodegeneration最新文献

{"title":"The molecular fidelity of Aβ pathology in 5xFAD and AppNL-FPsen1P117L mice revealed by cryo-EM.","authors":"Meinai Song,Hanrun Zheng,Jianting Han,Kaiyu Xu,Deng-Feng Zhang,Qin Cao","doi":"10.1186/s13024-026-00924-6","DOIUrl":"https://doi.org/10.1186/s13024-026-00924-6","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"3 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947457","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}

{"title":"Neuronal subtype governs amyloid structure, cellular response, and cognitive outcome in genetically targeted APP mouse models.","authors":"Gabriella A Perez,Zoe Lai,George A Edwards Iii,Jacob M Dundee,Shannon N Leahy,Chuangye Qi,Yanyan Qi,Ye-Jin Park,Tzu-Chiao Lu,M Danish Uddin,Rong Zhao,Hui Zheng,Hongjie Li,Joanna L Jankowsky","doi":"10.1186/s13024-025-00919-9","DOIUrl":"https://doi.org/10.1186/s13024-025-00919-9","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"15 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907800","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}

{"title":"OMG! A proteomic determinant of neurodegenerative resiliency.","authors":"Michael R Duggan,Hamilton Se-Hwee Oh,Philipp Frank,Gabriela T Gomez,David Zweibaum,Yuhan Cui,Jingsha Chen,Aditya Surapaneni,Cassandra O Blew,Heather E Dark,Cassandra M Joynes,Sridhar Kandala,Murat Bilgel,Amelia Farinas,Guray Erus,Qu Tian,Julián Candia,Krishna A Pucha,Bennett A Landman,Logan Dumitrescu,Timothy J Hohman,Alexandria Lewis,Abhay Moghekar,Fatemeh Siavoshi,Muhammad Ali,Menghan Liu,Ying Xu,Daniel Western,Naoto Kaneko,Shintaro Kato,Makio Furuichi,Masaki Shibayama,Masahisa Katsuno,Yukiko Nishita,Rei Otsuka,Rebecca F Gottesman,Eric B Dammer,Nicholas T Seyfried,Allan I Levey,Erik C B Johnson,Elizabeth Mormino,Anthony D Wagner,Kathleen L Poston,Dimitrios Kapogiannis,Morgan E Grams,Pavan Bhargava,Iwao Waga,Christos Davatzikos,Susan M Resnick,Luigi Ferrucci,David A Bennett,Carlos Cruchaga,Tony Wyss-Coray,Mika Kivimäki,Josef Coresh,Keenan A Walker","doi":"10.1186/s13024-025-00921-1","DOIUrl":"https://doi.org/10.1186/s13024-025-00921-1","url":null,"abstract":"BACKGROUNDBiofluid proteomics can enhance our understanding of the neurodegenerative mechanisms underlying Alzheimer's disease and related dementias (ADRDs). Oligodendrocyte myelin glycoprotein (OMG) is a brain-specific protein implicated in myelination, but its potential mechanistic, biomarker, and therapeutic roles in ADRDs requires further elucidation.METHODSAfter detecting an inverse association between its abundance in peripheral circulation and cortical amyloid deposition in two community-based cohorts, the current study characterized OMG's role in ADRDs with high-throughput proteomics from sixteen independent cohorts. Data included a variety of cross-sectional and longitudinal community-based and clinical cohorts from North America, Europe, and Asia, and incorporated complementary biofluids, biospecimens, and proteomic platforms. Statistical analyses were conducted separately in each cohort.RESULTSWe detected lower plasma OMG in individuals with cortical amyloid deposition, compromised brain structure, dementia, and multiple sclerosis, as well as in individuals who developed dementia over 7- to 20-year follow-up periods. OMG's CSF and brain proteomic signatures reflected broader neuroprotective mechanisms, especially axonal structural integrity, and two-sample Mendelian randomization causally implicated OMG as protective against multiple neurodegenerative diseases.CONCLUSIONSOur findings implicate OMG as a mechanistic determinant of neurodegenerative resiliency among older adults, which is reliably captured by its abundance in peripheral circulation.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"21 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903702","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}

{"title":"Developmental dopamine loss rewires striatal circuits to promote locomotion.","authors":"Jie Dong, Breanna T Sullivan, Victor M Martinez Smith, Lupeng Wang, Lulu Tian, Justin Kung, Bin Song, Shirong Lin, Andreanna Le, Lixin Sun, Lisa Chang, Jinhui Ding, Weidong Le, Jun Jia, Huaibin Cai","doi":"10.1186/s13024-025-00920-2","DOIUrl":"10.1186/s13024-025-00920-2","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":" ","pages":"7"},"PeriodicalIF":17.5,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12866494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896170","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}

{"title":"Organelle stress in NLRP3 inflammasome: a central mediator of neurodegenerative diseases.","authors":"Huachao Jia,Lianghua Ma,Jinyue Liu,Menglin Gao,Xuxin Liang,Fan Zhang,Yanzi Gao,Mingyan Liu,Wanwei Jiang,Minjie Wei,Xin Zhong","doi":"10.1186/s13024-025-00922-0","DOIUrl":"https://doi.org/10.1186/s13024-025-00922-0","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"262 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895391","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}

{"title":"Disrupting α-Synuclein-ClpP interaction restores mitochondrial function and attenuates neuropathology in Parkinson's disease models.","authors":"Di Hu,Xiaoyan Sun,Xin Qi","doi":"10.1186/s13024-025-00918-w","DOIUrl":"https://doi.org/10.1186/s13024-025-00918-w","url":null,"abstract":"BACKGROUNDMitochondrial dysfunction and α-Synuclein (αSyn) aggregation are defining features of Parkinson's disease (PD), yet the mechanistic link between them remains poorly understood. Although our previous findings suggest that the interaction between αSyn and ClpP (a mitochondrial matrix protease) contributes to PD progression, the pathogenic and therapeutic relevance of this interaction remains elusive.METHODSWe employed biochemical and cell biological approaches to investigate how αSyn and ClpP are mutually regulated. Additionally, we determined the pathogenic impact of αSyn-ClpP interaction by using decoy peptide CS2 in αSyn-PFF inoculated primary neurons, PD patient iPSC-derived dopaminergic neurons, and a transgenic mouse model of PD carrying αSyn-A53T mutation.RESULTSWe identified mitochondrial protease ClpP as a key regulator of αSyn pathology. We show that αSyn interacts with ClpP through its non-amyloid-β component (NAC) domain, leading to impaired ClpP activity and mitochondrial proteotoxic stress. ClpP, in turn, negatively regulates αSyn aggregation and propagation by stabilizing its native tetrameric form. To interrupt this pathogenic interaction, we developed a decoy peptide, CS2, which binds the NAC domain of αSyn and restores ClpP function. CS2 treatment reduced mitochondrial oxidative stress and αSyn neurotoxicity in neuronal cultures, primary cortical neurons inoculated with αSyn preformed fibrils, and dopaminergic neurons derived from PD patient iPSCs. In mThy1-hSNCA transgenic mice, subcutaneous administration of CS2 restored ClpP levels, decreased αSyn pathology and neuroinflammation, and improved both cognitive and motor function.CONCLUSIONThese findings highlight the αSyn-ClpP interaction as a druggable target and support CS2 as a potential disease-modifying therapy for PD and related synucleinopathies.","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"20 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807655","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}

{"title":"The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.","authors":"Maria-Tzousi Papavergi,Praveen Bathini,Brijendra Singh,Cynthia A Lemere","doi":"10.1186/s13024-025-00916-y","DOIUrl":"https://doi.org/10.1186/s13024-025-00916-y","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"21 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759968","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}

{"title":"Targeted deletion of EMMPRIN in microglia/macrophages mitigates neuronal death in intracerebral hemorrhage.","authors":"Zhe Li,Xiangyu Zhang,Maryam Mobarakabadi,Yang Liu,Ruixue Wei,Claudia Silva,Frank Visser,Antoine Dufour,Daniel Young,Deepak Kaushik,V Wee Yong,Mengzhou Xue","doi":"10.1186/s13024-025-00917-x","DOIUrl":"https://doi.org/10.1186/s13024-025-00917-x","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"232 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746707","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}

{"title":"The pesticide chlorpyrifos increases the risk of Parkinson's disease.","authors":"Kazi Md Mahmudul Hasan, Lisa M Barnhill, Kimberly C Paul, Chao Peng, William Zeiger, Beate Ritz, Marisol Arellano, Michael Ajnassian, Shujing Zhang, Aye Theint Theint, Gazmend Elezi, Hilli Weinberger, Julian P Whitelegge, Qing Bai, Sharon Li, Edward A Burton, Jeff M Bronstein","doi":"10.1186/s13024-025-00915-z","DOIUrl":"10.1186/s13024-025-00915-z","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":" ","pages":"3"},"PeriodicalIF":17.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12801438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743366","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}

{"title":"Diagnostic biomarkers for α-synucleinopathies- state of the art and future developments: a systematic review.","authors":"V Donadio,M Ingelsson,G Rizzo,A Furia,A Incensi,C Delprete,M Pinho,R Liguori,S Pritzkow","doi":"10.1186/s13024-025-00914-0","DOIUrl":"https://doi.org/10.1186/s13024-025-00914-0","url":null,"abstract":"","PeriodicalId":18800,"journal":{"name":"Molecular Neurodegeneration","volume":"204 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674411","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}