{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:08:25Z","timestamp":1793110105929,"version":"4.5.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1904207"],"award-info":[{"award-number":["U1904207"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2017YFA0105003"],"award-info":[{"award-number":["2017YFA0105003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences","award":["2020-PT310-01"],"award-info":[{"award-number":["2020-PT310-01"]}]},{"name":"Innovative and Scientific and Technological Talents Training Project of Henan Province","award":["YXKC2021062"],"award-info":[{"award-number":["YXKC2021062"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) are three nervous system diseases that partially overlap clinically and genetically. However, bulk RNA-sequencing did not accurately detect the core pathogenic molecules in them. The availability of high-quality single cell RNA-sequencing data of post-mortem brain collections permits the generation of a large-scale gene expression in different cells in human brain, focusing on the molecular features and relationships between diseases and genes. We integrated single-nucleus RNA-sequencing (snRNA-seq) datasets of human brains with AD, PD, and MS to identify transcriptomic commonalities and distinctions among them.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The snRNA-seq datasets were downloaded from Gene Expression Omnibus (GEO) database. The Seurat package was used for snRNA-seq data processing. The uniform manifold approximation and projection (UMAP) were utilized for cluster identification. The FindMarker function in Seurat was used to identify the differently expressed genes. Functional enrichment analysis was carried out using the Gene Set Enrichment Analysis (GSEA) and Gene ontology (GO). The protein\u2010protein interaction (PPI) analysis of differentially expressed genes (DEGs) was analyzed using STRING database (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/string-db.org\">http:\/\/string-db.org<\/jats:ext-link>). SCENIC analysis was performed using utilizing pySCENIC (v0.10.0) based on the hg19-tss-centered-10\u00a0kb-10species databases. The analysis of potential therapeutic drugs was analyzed on Connectivity Map (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clue.io\">https:\/\/clue.io<\/jats:ext-link>).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The gene regulatory network analysis identified several hub genes regulated in AD, PD, and MS, in which <jats:italic>HSPB1<\/jats:italic> and <jats:italic>HSPA1A<\/jats:italic> were key molecules. These upregulated HSP family genes interact with ribosome genes in AD and MS, and with immunomodulatory genes in PD. We further identified several transcriptional regulators (<jats:italic>SPI1<\/jats:italic>, <jats:italic>CEBPA<\/jats:italic>, <jats:italic>TFE3<\/jats:italic>, <jats:italic>GRHPR<\/jats:italic>, and <jats:italic>TP53<\/jats:italic>) of the hub genes, which has important implications for uncovering the molecular crosstalk among AD, PD, and MS. Arctigenin was identified as a potential therapeutic drug for AD, PD, and MS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Together, the integrated snRNA-seq data and findings have significant implications for unraveling the shared and unique molecular crosstalk among AD, PD, and MS. <jats:italic>HSPB1<\/jats:italic> and <jats:italic>HSPA1A<\/jats:italic> as promising targets involved in the pathological mechanisms of neurodegenerative diseases. Additionally, the identification of arctigenin as a potential therapeutic drug for AD, PD, and MS further highlights its potential in treating these neurological disorders. These discoveries lay the groundwork for future research and interventions to enhance our understanding and treatment of AD, PD, and MS.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-023-04516-6","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T17:01:42Z","timestamp":1695315702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Integrating single-nucleus sequence profiling to reveal the transcriptional dynamics of Alzheimer\u2019s disease, Parkinson\u2019s disease, and multiple sclerosis"],"prefix":"10.1186","volume":"21","author":[{"given":"Li-Yuan","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo-Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Yu","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2689-9897","authenticated-orcid":false,"given":"Yu-Ming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"issue":"2","key":"4516_CR1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ejhg.2012.129","volume":"21","author":"V Costa","year":"2013","unstructured":"Costa V, Aprile M, Esposito R, Ciccodicola A. RNA-Seq and human complex diseases: recent accomplishments and future perspectives. Eur J Hum Genet. 2013;21(2):134\u201342.","journal-title":"Eur J Hum Genet"},{"issue":"5","key":"4516_CR2","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1017\/S1355617798455024","volume":"4","author":"RD Nebes","year":"1998","unstructured":"Nebes RD, Halligan EM, Rosen J, Reynolds CF 3rd. Cognitive and motor slowing in Alzheimer\u2019s disease and geriatric depression. J Int Neuropsychol Soc. 1998;4(5):426\u201334.","journal-title":"J Int Neuropsychol Soc"},{"issue":"Suppl 1","key":"4516_CR3","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/jnc.13750","volume":"139","author":"W Oertel","year":"2016","unstructured":"Oertel W, Schulz JB. Current and experimental treatments of Parkinson disease: a guide for neuroscientists. J Neurochem. 2016;139(Suppl 1):325\u201337.","journal-title":"J Neurochem"},{"issue":"1","key":"4516_CR4","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00429-013-0665-9","volume":"220","author":"G Longoni","year":"2015","unstructured":"Longoni G, Rocca MA, Pagani E, Riccitelli GC, Colombo B, Rodegher M, Falini A, Comi G, Filippi M. Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS. Brain Struct Funct. 2015;220(1):435\u201344.","journal-title":"Brain Struct Funct"},{"issue":"9","key":"4516_CR5","doi-asserted-by":"crossref","first-page":"4958","DOI":"10.3390\/ijms22094958","volume":"22","author":"F Paolini Paoletti","year":"2021","unstructured":"Paolini Paoletti F, Simoni S, Parnetti L, Gaetani L. The contribution of small vessel disease to neurodegeneration: focus on Alzheimer\u2019s disease, Parkinson\u2019s disease and multiple sclerosis. Int J Mol Sci. 2021;22(9):4958.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"4516_CR6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.2174\/1567205010666131119235254","volume":"11","author":"E Lyros","year":"2014","unstructured":"Lyros E, Bakogiannis C, Liu Y, Fassbender K. Molecular links between endothelial dysfunction and neurodegeneration in Alzheimer\u2019s disease. Curr Alzheimer Res. 2014;11(1):18\u201326.","journal-title":"Curr Alzheimer Res"},{"issue":"7113","key":"4516_CR7","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nature05292","volume":"443","author":"MT Lin","year":"2006","unstructured":"Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443(7113):787\u201395.","journal-title":"Nature"},{"issue":"1","key":"4516_CR8","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.bbrc.2007.09.102","volume":"364","author":"HE Boycott","year":"2007","unstructured":"Boycott HE, Dallas M, Boyle JP, Pearson HA, Peers C. Hypoxia suppresses astrocyte glutamate transport independently of amyloid formation. Biochem Biophys Res Commun. 2007;364(1):100\u20134.","journal-title":"Biochem Biophys Res Commun"},{"issue":"4","key":"4516_CR9","doi-asserted-by":"crossref","first-page":"953","DOI":"10.3390\/molecules26040953","volume":"26","author":"F Piancone","year":"2021","unstructured":"Piancone F, La Rosa F, Marventano I, Saresella M, Clerici M. The role of the inflammasome in neurodegenerative diseases. Molecules. 2021;26(4):953.","journal-title":"Molecules"},{"issue":"3","key":"4516_CR10","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nprot.2016.015","volume":"11","author":"SR Krishnaswami","year":"2016","unstructured":"Krishnaswami SR, Grindberg RV, Novotny M, Venepally P, Lacar B, Bhutani K, Linker SB, Pham S, Erwin JA, Miller JA, et al. Using single nuclei for RNA-seq to capture the transcriptome of postmortem neurons. Nat Protoc. 2016;11(3):499\u2013524.","journal-title":"Nat Protoc"},{"issue":"1","key":"4516_CR11","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/nbt.4038","volume":"36","author":"BB Lake","year":"2018","unstructured":"Lake BB, Chen S, Sos BC, Fan J, Kaeser GE, Yung YC, Duong TE, Gao D, Chun J, Kharchenko PV, et al. Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain. Nat Biotechnol. 2018;36(1):70\u201380.","journal-title":"Nat Biotechnol"},{"issue":"12","key":"4516_CR12","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1038\/s41593-019-0539-4","volume":"22","author":"A Grubman","year":"2019","unstructured":"Grubman A, Chew G, Ouyang JF, Sun G, Choo XY, McLean C, Simmons RK, Buckberry S, Vargas-Landin DB, Poppe D, et al. A single-cell atlas of entorhinal cortex from individuals with Alzheimer\u2019s disease reveals cell-type-specific gene expression regulation. Nat Neurosci. 2019;22(12):2087\u201397.","journal-title":"Nat Neurosci"},{"issue":"8","key":"4516_CR13","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/s41588-021-00894-z","volume":"53","author":"S Morabito","year":"2021","unstructured":"Morabito S, Miyoshi E, Michael N, Shahin S, Martini AC, Head E, Silva J, Leavy K, Perez-Rosendahl M, Swarup V. Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer\u2019s disease. Nat Genet. 2021;53(8):1143\u201355.","journal-title":"Nat Genet"},{"issue":"3","key":"4516_CR14","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1093\/brain\/awab446","volume":"145","author":"S Smaji\u0107","year":"2022","unstructured":"Smaji\u0107 S, Prada-Medina CA, Landoulsi Z, Ghelfi J, Delcambre S, Dietrich C, Jarazo J, Henck J, Balachandran S, Pachchek S, et al. Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state. Brain. 2022;145(3):964\u201378.","journal-title":"Brain"},{"issue":"7745","key":"4516_CR15","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41586-019-0903-2","volume":"566","author":"S J\u00e4kel","year":"2019","unstructured":"J\u00e4kel S, Agirre E, Mendanha Falc\u00e3o A, van Bruggen D, Lee KW, Knuesel I, Malhotra D, Ffrench-Constant C, Williams A, Castelo-Branco G. Altered human oligodendrocyte heterogeneity in multiple sclerosis. Nature. 2019;566(7745):543\u20137.","journal-title":"Nature"},{"issue":"5","key":"4516_CR16","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36(5):411\u201320.","journal-title":"Nat Biotechnol"},{"issue":"43","key":"4516_CR17","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545\u201350.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"4516_CR18","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","volume":"14","author":"S Aibar","year":"2017","unstructured":"Aibar S, Gonz\u00e1lez-Blas CB, Moerman T, Huynh-Thu VA, Imrichova H, Hulselmans G, Rambow F, Marine JC, Geurts P, Aerts J, et al. SCENIC: single-cell regulatory network inference and clustering. Nat Methods. 2017;14(11):1083\u20136.","journal-title":"Nat Methods"},{"issue":"1","key":"4516_CR19","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nrc2044","volume":"7","author":"J Lamb","year":"2007","unstructured":"Lamb J. The Connectivity Map: a new tool for biomedical research. Nat Rev Cancer. 2007;7(1):54\u201360.","journal-title":"Nat Rev Cancer"},{"issue":"5795","key":"4516_CR20","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1126\/science.1132939","volume":"313","author":"J Lamb","year":"2006","unstructured":"Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, Lerner J, Brunet JP, Subramanian A, Ross KN, et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006;313(5795):1929\u201335.","journal-title":"Science"},{"issue":"7","key":"4516_CR21","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM 3rd, Hao Y, Stoeckius M, Smibert P, Satija R. Comprehensive integration of single-cell data. Cell. 2019;177(7):1888-1902.e1821.","journal-title":"Cell"},{"issue":"7","key":"4516_CR22","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-019-0101-y","volume":"20","author":"MS Hipp","year":"2019","unstructured":"Hipp MS, Kasturi P, Hartl FU. The proteostasis network and its decline in ageing. Nat Rev Mol Cell Biol. 2019;20(7):421\u201335.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"25","key":"4516_CR23","doi-asserted-by":"crossref","first-page":"18724","DOI":"10.1074\/jbc.M001981200","volume":"275","author":"C Liu","year":"2000","unstructured":"Liu C, Gilmont RR, Benndorf R, Welsh MJ. Identification and characterization of a novel protein from Sertoli cells, PASS1, that associates with mammalian small stress protein hsp27. J Biol Chem. 2000;275(25):18724\u201331.","journal-title":"J Biol Chem"},{"key":"4516_CR24","doi-asserted-by":"crossref","first-page":"1065654","DOI":"10.3389\/fphar.2022.1065654","volume":"13","author":"Y Li","year":"2022","unstructured":"Li Y, Lan X, Wang S, Cui Y, Song S, Zhou H, Li Q, Dai L, Zhang J. Serial five-membered lactone ring ions in the treatment of Alzheimer\u2019s diseases-comprehensive profiling of arctigenin metabolites and network analysis. Front Pharmacol. 2022;13:1065654.","journal-title":"Front Pharmacol"},{"issue":"32","key":"4516_CR25","doi-asserted-by":"crossref","first-page":"13138","DOI":"10.1523\/JNEUROSCI.4790-12.2013","volume":"33","author":"Z Zhu","year":"2013","unstructured":"Zhu Z, Yan J, Jiang W, Yao XG, Chen J, Chen L, Li C, Hu L, Jiang H, Shen X. Arctigenin effectively ameliorates memory impairment in Alzheimer\u2019s disease model mice targeting both \u03b2-amyloid production and clearance. J Neurosci. 2013;33(32):13138\u201349.","journal-title":"J Neurosci"},{"issue":"1","key":"4516_CR26","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1055\/s-0033-1360171","volume":"80","author":"D Li","year":"2014","unstructured":"Li D, Liu Q, Jia D, Dou D, Wang X, Kang T. Protective effect of arctigenin against MPP+ and MPTP-induced neurotoxicity. Planta Med. 2014;80(1):48\u201355.","journal-title":"Planta Med"},{"issue":"8","key":"4516_CR27","doi-asserted-by":"crossref","first-page":"5356","DOI":"10.1007\/s12035-015-9462-1","volume":"53","author":"W Li","year":"2016","unstructured":"Li W, Zhang Z, Zhang K, Xue Z, Li Y, Zhang Z, Zhang L, Gu C, Zhang Q, Hao J, et al. Arctigenin suppress Th17 cells and ameliorates experimental autoimmune encephalomyelitis through AMPK and PPAR-\u03b3\/ROR-\u03b3t signaling. Mol Neurobiol. 2016;53(8):5356\u201366.","journal-title":"Mol Neurobiol"},{"issue":"4","key":"4516_CR28","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s13760-016-0613-6","volume":"116","author":"LM Chi","year":"2016","unstructured":"Chi LM, Wang X, Nan GX. In silico analyses for molecular genetic mechanism and candidate genes in patients with Alzheimer\u2019s disease. Acta Neurol Belg. 2016;116(4):543\u20137.","journal-title":"Acta Neurol Belg"},{"key":"4516_CR29","first-page":"9480398","volume":"2022","author":"Y Dong","year":"2022","unstructured":"Dong Y, Li T, Ma Z, Zhou C, Wang X, Li J. HSPA1A, HSPA2, and hspa8 are potential molecular biomarkers for prognosis among HSP70 family in Alzheimer\u2019s Disease. Dis Markers. 2022;2022:9480398.","journal-title":"Dis Markers"},{"issue":"9","key":"4516_CR30","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.3390\/cells9091959","volume":"9","author":"S Muraoka","year":"2020","unstructured":"Muraoka S, Jedrychowski MP, Yanamandra K, Ikezu S, Gygi SP, Ikezu T. Proteomic profiling of extracellular vesicles derived from cerebrospinal fluid of Alzheimer\u2019s disease patients: a pilot study. Cells. 2020;9(9):1959.","journal-title":"Cells"},{"key":"4516_CR31","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1007\/s10072-023-06738-4","volume":"44","author":"L Asad Samani","year":"2023","unstructured":"Asad Samani L, Ghaedi K, Majd A, Peymani M, Etemadifar M. Coordinated modification in expression levels of HSPA1A\/B, DGKH, and NOTCH2 in Parkinson\u2019s patients\u2019 blood and substantia nigra as a diagnostic sign: the transcriptomes\u2019 relationship. Neurol Sci. 2023;44:2753.","journal-title":"Neurol Sci"},{"key":"4516_CR32","volume":"13","author":"J Huang","year":"2022","unstructured":"Huang J, Liu L, Qin L, Huang H, Li X. Single-cell transcriptomics uncovers cellular heterogeneity, mechanisms, and therapeutic targets for Parkinson\u2019s disease. Front Genet. 2022;13: 686739.","journal-title":"Front Genet"},{"issue":"1","key":"4516_CR33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40478-019-0660-3","volume":"7","author":"H Gerber","year":"2019","unstructured":"Gerber H, Mosser S, Boury-Jamot B, Stumpe M, Piersigilli A, Goepfert C, Dengjel J, Albrecht U, Magara F, Fraering PC. The APMAP interactome reveals new modulators of APP processing and beta-amyloid production that are altered in Alzheimer\u2019s disease. Acta Neuropathol Commun. 2019;7(1):13.","journal-title":"Acta Neuropathol Commun"},{"key":"4516_CR34","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fnmol.2015.00040","volume":"8","author":"RM Hussein","year":"2015","unstructured":"Hussein RM, Hashem RM, Rashed LA. Evaluation of the amyloid beta-GFP fusion protein as a model of amyloid beta peptides-mediated aggregation: a study of DNAJB6 chaperone. Front Mol Neurosci. 2015;8:40.","journal-title":"Front Mol Neurosci"},{"issue":"4","key":"4516_CR35","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.3233\/JAD-170398","volume":"59","author":"MB Evgen'ev","year":"2017","unstructured":"Evgen\u2019ev MB, Krasnov GS, Nesterova IV, Garbuz DG, Karpov VL, Morozov AV, Snezhkina AV, Samokhin AN, Sergeev A, Kulikov AM, et al. Molecular mechanisms underlying neuroprotective effect of intranasal administration of human Hsp70 in mouse model of Alzheimer\u2019s disease. J Alzheimers Dis. 2017;59(4):1415\u201326.","journal-title":"J Alzheimers Dis"},{"key":"4516_CR36","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.expneurol.2018.04.012","volume":"306","author":"IV Ekimova","year":"2018","unstructured":"Ekimova IV, Plaksina DV, Pastukhov YF, Lapshina KV, Lazarev VF, Mikhaylova ER, Polonik SG, Pani B, Margulis BA, Guzhova IV, et al. New HSF1 inducer as a therapeutic agent in a rodent model of Parkinson\u2019s disease. Exp Neurol. 2018;306:199\u2013208.","journal-title":"Exp Neurol"},{"issue":"1","key":"4516_CR37","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ymthe.2004.09.007","volume":"11","author":"Z Dong","year":"2005","unstructured":"Dong Z, Wolfer DP, Lipp HP, B\u00fceler H. Hsp70 gene transfer by adeno-associated virus inhibits MPTP-induced nigrostriatal degeneration in the mouse model of Parkinson disease. Mol Ther. 2005;11(1):80\u20138.","journal-title":"Mol Ther"},{"issue":"3","key":"4516_CR38","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/NEN.0b013e318165b239","volume":"67","author":"AN Mh\u00e1ille","year":"2008","unstructured":"Mh\u00e1ille AN, McQuaid S, Windebank A, Cunnea P, McMahon J, Samali A, FitzGerald U. Increased expression of endoplasmic reticulum stress-related signaling pathway molecules in multiple sclerosis lesions. J Neuropathol Exp Neurol. 2008;67(3):200\u201311.","journal-title":"J Neuropathol Exp Neurol"},{"key":"4516_CR39","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3389\/fnins.2015.00264","volume":"9","author":"S Stone","year":"2015","unstructured":"Stone S, Lin W. The unfolded protein response in multiple sclerosis. Front Neurosci. 2015;9:264.","journal-title":"Front Neurosci"},{"key":"4516_CR40","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s40478-015-0267-2","volume":"3","author":"LA Peferoen","year":"2015","unstructured":"Peferoen LA, Gerritsen WH, Breur M, Ummenthum KM, Peferoen-Baert RM, van der Valk P, van Noort JM, Amor S. Small heat shock proteins are induced during multiple sclerosis lesion development in white but not grey matter. Acta Neuropathol Commun. 2015;3:87.","journal-title":"Acta Neuropathol Commun"},{"issue":"2\u20133","key":"4516_CR41","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/pmic.201400189","volume":"15","author":"EB Dammer","year":"2015","unstructured":"Dammer EB, Lee AK, Duong DM, Gearing M, Lah JJ, Levey AI, Seyfried NT. Quantitative phosphoproteomics of Alzheimer\u2019s disease reveals cross-talk between kinases and small heat shock proteins. Proteomics. 2015;15(2\u20133):508\u201319.","journal-title":"Proteomics"},{"issue":"19","key":"4516_CR42","doi-asserted-by":"crossref","first-page":"9671","DOI":"10.1073\/pnas.1818347116","volume":"116","author":"E Kotelnikova","year":"2019","unstructured":"Kotelnikova E, Kiani NA, Messinis D, Pertsovskaya I, Pliaka V, Bernardo-Faura M, Rinas M, Vila G, Zubizarreta I, Pulido-Valdeolivas I, et al. MAPK pathway and B cells overactivation in multiple sclerosis revealed by phosphoproteomics and genomic analysis. Proc Natl Acad Sci USA. 2019;116(19):9671\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"17","key":"4516_CR43","doi-asserted-by":"crossref","first-page":"12778","DOI":"10.1074\/jbc.M109.082644","volume":"285","author":"L Almeida-Souza","year":"2010","unstructured":"Almeida-Souza L, Goethals S, de Winter V, Dierick I, Gallardo R, Van Durme J, Irobi J, Gettemans J, Rousseau F, Schymkowitz J, et al. Increased monomerization of mutant HSPB1 leads to protein hyperactivity in Charcot-Marie-Tooth neuropathy. J Biol Chem. 2010;285(17):12778\u201386.","journal-title":"J Biol Chem"},{"issue":"27","key":"4516_CR44","doi-asserted-by":"crossref","first-page":"18947","DOI":"10.1074\/jbc.274.27.18947","volume":"274","author":"T Rogalla","year":"1999","unstructured":"Rogalla T, Ehrnsperger M, Preville X, Kotlyarov A, Lutsch G, Ducasse C, Paul C, Wieske M, Arrigo AP, Buchner J, et al. Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress\/tumor necrosis factor alpha by phosphorylation. J Biol Chem. 1999;274(27):18947\u201356.","journal-title":"J Biol Chem"},{"issue":"20","key":"4516_CR45","doi-asserted-by":"crossref","first-page":"15168","DOI":"10.1016\/S0021-9258(18)82451-6","volume":"268","author":"C Faucher","year":"1993","unstructured":"Faucher C, Capdevielle J, Canal I, Ferrara P, Mazarguil H, McGuire WL, Darbon JM. The 28-kDa protein whose phosphorylation is induced by protein kinase C activators in MCF-7 cells belongs to the family of low molecular mass heat shock proteins and is the estrogen-regulated 24-kDa protein. J Biol Chem. 1993;268(20):15168\u201373.","journal-title":"J Biol Chem"},{"issue":"1","key":"4516_CR46","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00401-013-1133-6","volume":"126","author":"A Holmgren","year":"2013","unstructured":"Holmgren A, Bouhy D, De Winter V, Asselbergh B, Timmermans JP, Irobi J, Timmerman V. Charcot-Marie-Tooth causing HSPB1 mutations increase Cdk5-mediated phosphorylation of neurofilaments. Acta Neuropathol. 2013;126(1):93\u2013108.","journal-title":"Acta Neuropathol"},{"issue":"2","key":"4516_CR47","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1152\/physrev.2001.81.2.741","volume":"81","author":"DJ Selkoe","year":"2001","unstructured":"Selkoe DJ. Alzheimer\u2019s disease: genes, proteins, and therapy. Physiol Rev. 2001;81(2):741\u201366.","journal-title":"Physiol Rev"},{"issue":"15","key":"4516_CR48","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1128\/MCB.01187-10","volume":"31","author":"J Ojha","year":"2011","unstructured":"Ojha J, Masilamoni G, Dunlap D, Udoff RA, Cashikar AG. Sequestration of toxic oligomers by HspB1 as a cytoprotective mechanism. Mol Cell Biol. 2011;31(15):3146\u201357.","journal-title":"Mol Cell Biol"},{"issue":"6","key":"4516_CR49","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s12192-013-0428-9","volume":"18","author":"ME T\u00f3th","year":"2013","unstructured":"T\u00f3th ME, Szegedi V, Varga E, Juh\u00e1sz G, Horv\u00e1th J, Borb\u00e9ly E, Csibr\u00e1ny B, Alf\u00f6ldi R, L\u00e9n\u00e1rt N, Penke B, et al. Overexpression of Hsp27 ameliorates symptoms of Alzheimer\u2019s disease in APP\/PS1 mice. Cell Stress Chaperones. 2013;18(6):759\u201371.","journal-title":"Cell Stress Chaperones"},{"issue":"8","key":"4516_CR50","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1074\/jbc.M117.803411","volume":"293","author":"HER Baughman","year":"2018","unstructured":"Baughman HER, Clouser AF, Klevit RE, Nath A. HspB1 and Hsc70 chaperones engage distinct tau species and have different inhibitory effects on amyloid formation. J Biol Chem. 2018;293(8):2687\u2013700.","journal-title":"J Biol Chem"},{"issue":"46","key":"4516_CR51","doi-asserted-by":"crossref","first-page":"15374","DOI":"10.1523\/JNEUROSCI.3155-10.2010","volume":"30","author":"JF Abisambra","year":"2010","unstructured":"Abisambra JF, Blair LJ, Hill SE, Jones JR, Kraft C, Rogers J, Koren J 3rd, Jinwal UK, Lawson L, Johnson AG, et al. Phosphorylation dynamics regulate Hsp27-mediated rescue of neuronal plasticity deficits in tau transgenic mice. J Neurosci. 2010;30(46):15374\u201382.","journal-title":"J Neurosci"},{"issue":"4","key":"4516_CR52","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s12192-017-0785-x","volume":"22","author":"D Cox","year":"2017","unstructured":"Cox D, Ecroyd H. The small heat shock proteins \u03b1B-crystallin (HSPB5) and Hsp27 (HSPB1) inhibit the intracellular aggregation of \u03b1-synuclein. Cell Stress Chaperones. 2017;22(4):589\u2013600.","journal-title":"Cell Stress Chaperones"},{"issue":"12","key":"4516_CR53","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1074\/jbc.M117.813865","volume":"293","author":"D Cox","year":"2018","unstructured":"Cox D, Whiten DR, Brown JWP, Horrocks MH, San Gil R, Dobson CM, Klenerman D, van Oijen AM, Ecroyd H. The small heat shock protein Hsp27 binds \u03b1-synuclein fibrils, preventing elongation and cytotoxicity. J Biol Chem. 2018;293(12):4486\u201397.","journal-title":"J Biol Chem"},{"issue":"7","key":"4516_CR54","first-page":"E1243","volume":"114","author":"Y Shi","year":"2017","unstructured":"Shi Y, Jiang X, Zhang L, Pu H, Hu X, Zhang W, Cai W, Gao Y, Leak RK, Keep RF, et al. Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood-brain barrier disruption after ischemic brain injury. Proc Natl Acad Sci USA. 2017;114(7):E1243-e1252.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"4516_CR55","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2174\/1871527311312030006","volume":"12","author":"RK Leak","year":"2013","unstructured":"Leak RK, Zhang L, Stetler RA, Weng Z, Li P, Atkins GB, Gao Y, Chen J. HSP27 protects the blood-brain barrier against ischemia-induced loss of integrity. CNS Neurol Disord Drug Targets. 2013;12(3):325\u201337.","journal-title":"CNS Neurol Disord Drug Targets"},{"issue":"12","key":"4516_CR56","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1111\/j.0013-9580.2004.14904.x","volume":"45","author":"HJ Bidmon","year":"2004","unstructured":"Bidmon HJ, G\u00f6rg B, Palomero-Gallagher N, Behne F, Lahl R, Pannek HW, Speckmann EJ, Zilles K. Heat shock protein-27 is upregulated in the temporal cortex of patients with epilepsy. Epilepsia. 2004;45(12):1549\u201359.","journal-title":"Epilepsia"},{"issue":"5","key":"4516_CR57","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrn1387","volume":"5","author":"C Iadecola","year":"2004","unstructured":"Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer\u2019s disease. Nat Rev Neurosci. 2004;5(5):347\u201360.","journal-title":"Nat Rev Neurosci"},{"key":"4516_CR58","volume":"72","author":"M Zhao","year":"2021","unstructured":"Zhao M, Jiang XF, Zhang HQ, Sun JH, Pei H, Ma LN, Cao Y, Li H. Interactions between glial cells and the blood-brain barrier and their role in Alzheimer\u2019s disease. Ageing Res Rev. 2021;72: 101483.","journal-title":"Ageing Res Rev"},{"issue":"2","key":"4516_CR59","doi-asserted-by":"crossref","first-page":"272","DOI":"10.2741\/4206","volume":"19","author":"H Lee","year":"2014","unstructured":"Lee H, Pienaar IS. Disruption of the blood-brain barrier in Parkinson\u2019s disease: curse or route to a cure? Front Biosci (Landmark Ed). 2014;19(2):272\u201380.","journal-title":"Front Biosci (Landmark Ed)"},{"issue":"8","key":"4516_CR60","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.arcmed.2014.11.013","volume":"45","author":"GG Ortiz","year":"2014","unstructured":"Ortiz GG, Pacheco-Mois\u00e9s FP, Mac\u00edas-Islas M, Flores-Alvarado LJ, Mireles-Ram\u00edrez MA, Gonz\u00e1lez-Renovato ED, Hern\u00e1ndez-Navarro VE, S\u00e1nchez-L\u00f3pez AL, Alatorre-Jim\u00e9nez MA. Role of the blood-brain barrier in multiple sclerosis. Arch Med Res. 2014;45(8):687\u201397.","journal-title":"Arch Med Res"},{"issue":"4","key":"4516_CR61","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1600-0404.1990.tb01563.x","volume":"81","author":"K Blennow","year":"1990","unstructured":"Blennow K, Wallin A, Fredman P, Karlsson I, Gottfries CG, Svennerholm L. Blood-brain barrier disturbance in patients with Alzheimer\u2019s disease is related to vascular factors. Acta Neurol Scand. 1990;81(4):323\u20136.","journal-title":"Acta Neurol Scand"},{"issue":"3","key":"4516_CR62","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/ana.20592","volume":"58","author":"M Lee","year":"2005","unstructured":"Lee M, Bard F, Johnson-Wood K, Lee C, Hu K, Griffith SG, Black RS, Schenk D, Seubert P. Abeta42 immunization in Alzheimer\u2019s disease generates Abeta N-terminal antibodies. Ann Neurol. 2005;58(3):430\u20135.","journal-title":"Ann Neurol"},{"issue":"11","key":"4516_CR63","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1177\/0271678X221111602","volume":"42","author":"M Suzuki","year":"2022","unstructured":"Suzuki M, Tezuka K, Handa T, Sato R, Takeuchi H, Takao M, Tano M, Uchida Y. Upregulation of ribosome complexes at the blood-brain barrier in Alzheimer\u2019s disease patients. J Cereb Blood Flow Metab. 2022;42(11):2134\u201350.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"4516_CR64","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12915-019-0664-2","volume":"17","author":"D Awad","year":"2019","unstructured":"Awad D, Prattes M, Kofler L, R\u00f6ssler I, Loibl M, Pertl M, Zisser G, Wolinski H, Pertschy B, Bergler H. Inhibiting eukaryotic ribosome biogenesis. BMC Biol. 2019;17(1):46.","journal-title":"BMC Biol"},{"issue":"11","key":"4516_CR65","first-page":"1641","volume":"41","author":"F Mu","year":"2021","unstructured":"Mu F, Chen X, Du X, Jiao Q, Bi M, Jiang H. Regulatory mechanism of interferon regulatory factor 1 by \u03b1-synuclein in mouse Parkinson\u2019s disease model. Nan Fang Yi Ke Da Xue Xue Bao. 2021;41(11):1641\u20138.","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04516-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-023-04516-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04516-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T22:11:54Z","timestamp":1700518314000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-023-04516-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,21]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["4516"],"URL":"https:\/\/doi.org\/10.1186\/s12967-023-04516-6","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,21]]},"assertion":[{"value":"15 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"No authors had conflicts of interests relevant to this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"649"}}