{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:56:37Z","timestamp":1792788997086,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. National Institutes of Health","award":["EY031674"],"award-info":[{"award-number":["EY031674"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"crossref"}]},{"name":"U.S. National Institutes of Health","award":["EY030081"],"award-info":[{"award-number":["EY030081"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"crossref"}]},{"award":["EY031674"],"award-info":[{"award-number":["EY031674"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["EY030081"],"award-info":[{"award-number":["EY030081"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of Missouri School of Medicine TRIUMPH program","id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Edwards School of Medicine at Marshall University","id":[{"id":"https:\/\/ror.org\/02erqft81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["P20GM103434"],"award-info":[{"award-number":["P20GM103434"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]},{"award":["P20GM103434"],"award-info":[{"award-number":["P20GM103434"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>CLN2 disease is a fatal lysosomal storage disorder caused by deficiency of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1), resulting in progressive neurodegeneration and non-neuronal pathology. While enzyme replacement therapy has improved disease management, there remains a critical need for objective molecular biomarkers capable of monitoring disease progression and therapeutic response. The purpose of this study was to utilize a canine model of CLN2 disease to investigate proteomic changes in cerebrospinal fluid (CSF) and in minimally invasive biofluids tears and plasma to identify candidate disease biomarkers. Untargeted proteomic analysis was conducted using these biofluids from unaffected controls and CLN2-affected dogs at presymptomatic, symptomatic, and advanced disease stages. CSF demonstrated the greatest degree of proteomic alterations over the disease progression. Proteins associated with cytoskeletal organization, synaptic signaling, lysosomal biology, mitochondrial metabolism, lipid homeostasis, and inflammatory responses were significantly altered. Tear fluid demonstrated overlapping biological themes with CSF, particularly involving mitochondrial metabolism, lysosomal function, and lipid-associated pathways. In contrast, plasma proteomic alterations were comparatively modest but supported systemic changes associated with extracellular signaling, inflammation, and lipid metabolism. Collectively, these findings demonstrate progressive and coordinated proteomic alterations across multiple biofluids in CLN2 disease that can serve as candidate biomarkers of disease progression.<\/jats:p>","DOI":"10.3390\/biology15191761","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:50:38Z","timestamp":1790959838000},"page":"1761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biofluid Proteomic Biomarker Discovery in a Large Animal Model of CLN2 Neuronal Ceroid Lipofuscinosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5560-6005","authenticated-orcid":false,"given":"Brandie R.","family":"Morgan-Jack","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace R.","family":"Kick","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"},{"name":"Christopher S. Bond Life Science Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-4924","authenticated-orcid":false,"given":"Trupti","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"},{"name":"Christopher S. Bond Life Science Center, University of Missouri, Columbia, MO 65211, USA"},{"name":"MU Institute for Data Science and Informatics, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Biomedical Informatics, Biostatistics and Medical Epidemiology, School of Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Brian","family":"Mooney","sequence":"additional","affiliation":[{"name":"Gehrke Proteomics Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-5528","authenticated-orcid":false,"given":"Joan R.","family":"Coates","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine & Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2616-5183","authenticated-orcid":false,"given":"Juri","family":"Ota-Kuroki","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine & Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2582-9187","authenticated-orcid":false,"given":"Martin L.","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca E. H.","family":"Whiting","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ismail, I.T., Showalter, M.R., and Fiehn, O. (2019). Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics. Metabolites, 9.","DOI":"10.3390\/metabo9100242"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.bbadis.2012.08.012","article-title":"The neuronal ceroid-lipofuscinoses: A historical introduction","volume":"1832","author":"Haltia","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/s41582-025-01132-4","article-title":"Neuronal ceroid lipofuscinosis: Underlying mechanisms and emerging therapeutic targets","volume":"21","author":"Takahashi","year":"2025","journal-title":"Nat. Rev. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/j.bbadis.2015.05.011","article-title":"Genetics of the neuronal ceroid lipofuscinoses (Batten disease)","volume":"1852","author":"Mole","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chang, M., Cooper, J.D., Davidson, B.L., van Diggelen, O.P., Elleder, M., Goebel, H.H., Golabek, A.A., Kida, E., Kohlsch\u00fctter, A., and Lobel, P. (2011). CLN2. The Neuronal Ceroid Lipofuscinoses (Batten Disease), Oxford University Press.","DOI":"10.1093\/med\/9780199590018.003.0007"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/ajmg.10660","article-title":"Late infantile neuronal ceroid lipofuscinosis: Quantitative description of the clinical course in patients with CLN2 mutations","volume":"112","author":"Steinfeld","year":"2002","journal-title":"Am. J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.bbadis.2012.11.014","article-title":"Human pathology in NCL","volume":"1832","author":"Anderson","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ymgme.2006.02.016","article-title":"A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile Dachshund with neuronal ceroid lipofuscinosis","volume":"89","author":"Awano","year":"2006","journal-title":"Mol. Genet. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/jnr.23423","article-title":"Enzyme replacement therapy attenuates disease progression in a canine model of late-infantile neuronal ceroid lipofuscinosis (CLN2 disease)","volume":"92","author":"Katz","year":"2014","journal-title":"J. Neurosci. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.ymgme.2014.09.004","article-title":"Nonclinical evaluation of CNS-administered TPP1 enzyme replacement in canine CLN2 neuronal ceroid lipofuscinosis","volume":"114","author":"Vuillemenot","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.exer.2014.06.008","article-title":"Enzyme replacement therapy delays pupillary light reflex deficits in a canine model of late infantile neuronal ceroid lipofuscinosis","volume":"125","author":"Whiting","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1007\/s40265-017-0771-8","article-title":"Cerliponase Alfa: First Global Approval","volume":"77","author":"Markham","year":"2017","journal-title":"Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"108135","DOI":"10.1016\/j.exer.2020.108135","article-title":"Intravitreal enzyme replacement inhibits progression of retinal degeneration in canine CLN2 neuronal ceroid lipofuscinosis","volume":"198","author":"Whiting","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"108130","DOI":"10.1016\/j.exer.2020.108130","article-title":"Intravitreal enzyme replacement preserves retinal structure and function in canine CLN2 neuronal ceroid lipofuscinosis","volume":"197","author":"Whiting","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15229","DOI":"10.1038\/s41598-018-33449-0","article-title":"Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease)","volume":"8","author":"Sindelar","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/febs.13593","article-title":"Plasma biomarkers for neuronal ceroid lipofuscinosis","volume":"283","author":"Hersrud","year":"2016","journal-title":"FEBS J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"165498","DOI":"10.1016\/j.bbadis.2019.06.012","article-title":"Applying modern Omic technologies to the Neuronal Ceroid Lipofuscinoses","volume":"1866","author":"Kline","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3787","DOI":"10.1021\/acs.jproteome.7b00460","article-title":"Proteomic Analysis of Brain and Cerebrospinal Fluid from the Three Major Forms of Neuronal Ceroid Lipofuscinosis Reveals Potential Biomarkers","volume":"16","author":"Sleat","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1074\/mcp.RA119.001587","article-title":"Analysis of Brain and cerebrospinal fluid from mouse models of the three major forms of neuronal ceroid lipofuscinosis reveals changes in the lysosomal proteome","volume":"18","author":"Sleat","year":"2019","journal-title":"Mol. Cell. Proteom."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103403","DOI":"10.1016\/j.jprot.2019.103403","article-title":"Proteomics characterization of extracellular vesicles sorted by flow cytometry reveals a disease-specific molecular cross-talk from cerebrospinal fluid and tears in multiple sclerosis","volume":"204","author":"Pieragostino","year":"2019","journal-title":"J. Proteom."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neulet.2013.08.019","article-title":"Tear levels of tumor necrosis factor-alpha in patients with Parkinson\u2019s disease","volume":"553","author":"Acar","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.baga.2015.05.001","article-title":"Biomarker sources for Parkinson\u2019s disease: Time to shed tears?","volume":"5","author":"Funke","year":"2015","journal-title":"Basal Ganglia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/prca.201300053","article-title":"Exploring the human tear fluid: Discovery of new biomarkers in multiple sclerosis","volume":"8","author":"Salvisberg","year":"2014","journal-title":"Proteom. Clin. Appl."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Winiarczyk, D., and Winiarczyk, M. (2026). Proteomic Analysis of Tear Film in Dogs and Cats: Emerging Biomarkers of Cognitive Dysfunction and Neurodegenerative Disorders. Animals, 16.","DOI":"10.3390\/ani16060930"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/vop.12502","article-title":"Tear fluid collection in dogs and cats using ophthalmic sponges","volume":"21","author":"Sebbag","year":"2018","journal-title":"Vet. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1002\/med.21716","article-title":"An eye on the dog as the scientist\u2019s best friend for translational research in ophthalmology: Focus on the ocular surface","volume":"40","author":"Sebbag","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eadf9717","DOI":"10.1126\/sciadv.adf9717","article-title":"A simple, time- and cost-effective, high-throughput depletion strategy for deep plasma proteomics","volume":"9","author":"Viode","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1038\/s41592-020-00998-0","article-title":"diaPASEF: Parallel accumulation\u2013serial fragmentation combined with data-independent acquisition","volume":"17","author":"Meier","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"gkaf018","DOI":"10.1093\/nar\/gkaf018","article-title":"edgeR 4.0: Powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets","volume":"53","author":"Chen","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"W207","DOI":"10.1093\/nar\/gkad347","article-title":"g:Profiler\u2014Interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update)","volume":"51","author":"Kolberg","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rohart, F., Gautier, B., Singh, A., and L\u00ea Cao, K.-A. (2017). mixOmics: An R package for \u2018omics feature selection and multiple data integration. PLoS Comput. Biol., 13.","DOI":"10.1101\/108597"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zeng, S., Lyu, Z., Narisetti, S.R.K., Xu, D., and Joshi, T. (2019). Knowledge Base Commons (KBCommons) v1.1: A universal framework for multi-omics data integration and biological discoveries. BMC Genom., 20.","DOI":"10.1186\/s12864-019-6287-8"},{"key":"ref_33","first-page":"100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ymeth.2019.06.013","article-title":"IMPRes-Pro: A high dimensional multiomics integration method for in silico hypothesis generation","volume":"173","author":"Jiang","year":"2020","journal-title":"Methods"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Liang, Y., Wang, D., Xu, D., and Joshi, T. (2017, January 13\u201316). IMPRes: Integrative MultiOmics pathway resolution algorithm and tool. Proceedings of the 2017 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), Kansas City, MO, USA.","DOI":"10.1109\/BIBM.2017.8218016"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"313ra180","DOI":"10.1126\/scitranslmed.aac6191","article-title":"AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease","volume":"7","author":"Katz","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2460\/ajvr.2005.66.67","article-title":"Assessment of retinal function and characterization of lysosomal storage body accumulation in the retinas and brains of Tibetan Terriers with ceroid-lipofuscinosis","volume":"66","author":"Katz","year":"2005","journal-title":"Am. J. Vet. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1167\/iovs.08-1712","article-title":"Retinal pathology in a canine model of late infantile neuronal ceroid lipofuscinosis","volume":"49","author":"Katz","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5432","DOI":"10.1167\/iovs.13-12012","article-title":"Quantitative Assessment of the Canine Pupillary Light Reflex","volume":"54","author":"Whiting","year":"2013","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.exer.2015.02.012","article-title":"Multifocal retinopathy in Dachshunds with CLN2 neuronal ceroid lipofuscinosis","volume":"134","author":"Whiting","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"564534","DOI":"10.1155\/2013\/564534","article-title":"Neuroprotective Function of 14-3-3 Proteins in Neurodegeneration","volume":"2013","author":"Shimada","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e213418","DOI":"10.1212\/WNL.0000000000213418","article-title":"What Is the Function and Relevance of 14-3-3 Proteins in Neurologic Disease?","volume":"104","author":"Benarroch","year":"2025","journal-title":"Neurology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1042\/bj2750269","article-title":"Lysosomal storage of subunit c of mitochondrial ATP synthase in Batten\u2019s disease (ceroid-lipofuscinosis)","volume":"275","author":"Hall","year":"1991","journal-title":"Biochem. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1002\/acn3.50942","article-title":"Neurofilament light is a treatment-responsive biomarker in CLN2 disease","volume":"6","author":"Ru","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"614","DOI":"10.12688\/f1000research.54556.1","article-title":"Cerebrospinal fluid neurofilament light levels in CLN2 disease patients treated with enzyme replacement therapy normalise after two years on treatment","volume":"10","author":"Iwan","year":"2021","journal-title":"F1000Research"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1021\/acs.jproteome.3c00199","article-title":"Cerebrospinal Fluid Protein Biomarker Discovery in CLN3","volume":"22","author":"Do","year":"2023","journal-title":"J. Proteome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1056\/NEJMoa1712649","article-title":"Study of Intraventricular Cerliponase Alfa for CLN2 Disease","volume":"378","author":"Schulz","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"102020","DOI":"10.1016\/j.isci.2020.102020","article-title":"Urine proteomics analysis of patients with neuronal ceroid lipofuscinoses","volume":"24","author":"Iwan","year":"2021","journal-title":"iScience"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"106349","DOI":"10.1016\/j.nbd.2023.106349","article-title":"Integrative human and murine multi-omics: Highlighting shared biomarkers in the neuronal ceroid lipofuscinoses","volume":"189","author":"Gammaldi","year":"2023","journal-title":"Neurobiol. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100590","DOI":"10.1016\/j.cophys.2022.100590","article-title":"Mechanisms controlling selective elimination of damaged lysosomes","volume":"29","author":"Hoyer","year":"2022","journal-title":"Curr. Opin. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1023\/A:1021036506299","article-title":"Altered Mitochondrial Function in Canine Ceroid-Lipofuscinosis","volume":"23","author":"Siakotos","year":"1998","journal-title":"Neurochem. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0197-0186(01)00128-0","article-title":"Mitochondrial dysfunction in the neuronal ceroid-lipofuscinoses (Batten disease)","volume":"40","author":"Jolly","year":"2002","journal-title":"Neurochem. Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.molmed.2016.12.003","article-title":"Mitochondrial Dysfunction and Neurodegeneration in Lysosomal Storage Disorders","volume":"23","author":"Plotegher","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12929-026-01253-y","article-title":"Modeling CLN3 Batten disease in astrocytes reveals alterations in mitochondria homeostasis, fatty acid metabolism and oxidative stress response","volume":"33","author":"Yang","year":"2026","journal-title":"J. Biomed. 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