{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:05:08Z","timestamp":1788537908003,"version":"build-2803163510"},"reference-count":196,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: The incidence of neurological disorders is increasing due to population growth and extended life expectancy. Despite advances in the understanding of these disorders, curative strategies for treatment have not yet eventuated. In part, this is due to the complexities of the disorders and a lack of identification of their specific underlying pathologies. Dictyostelium discoideum has provided a useful, simple model to aid in unraveling the complex pathological characteristics of neurological disorders including Alzheimer\u2019s disease, Parkinson\u2019s disease, Huntington\u2019s disease, neuronal ceroid lipofuscinoses and lissencephaly. In addition, D. discoideum has proven to be an innovative model for pharmaceutical research in the neurological field. Scope of review: This review describes the contributions of D. discoideum in the field of neurological research. The continued exploration of proteins implicated in neurological disorders in D. discoideum may elucidate their pathological roles and fast-track curative therapeutics.<\/jats:p>","DOI":"10.3390\/cells11030463","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T01:41:59Z","timestamp":1643420519000},"page":"463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dictyostelium discoideum: A Model System for Neurological Disorders"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3842-1284","authenticated-orcid":false,"given":"Claire Louise","family":"Storey","sequence":"first","affiliation":[{"name":"Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9826-6020","authenticated-orcid":false,"given":"Robin Simon Brooke","family":"Williams","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London, Egham TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1884-6306","authenticated-orcid":false,"given":"Paul Robert","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7604-3985","authenticated-orcid":false,"given":"Sarah Jane","family":"Annesley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000495197","article-title":"Global Burden of Neurological Disorders: From Global Burden of Disease Estimates to Actions","volume":"52","author":"Feigin","year":"2019","journal-title":"Neuroepidemiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.bbagen.2013.10.019","article-title":"Dictyostelium, a microbial model for brain disease","volume":"1840","author":"Annesley","year":"2014","journal-title":"BBA-Gen. Subj."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Annesley, S.J., and Fisher, P.R. (2021). Lymphoblastoid Cell Lines as Models to Study Mitochondrial Function in Neurological Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094536"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"dmm046110","DOI":"10.1242\/dmm.046110","article-title":"Caldwell. Modeling neurodegeneration in Caenorhabditis elegans","volume":"13","author":"Caldwell","year":"2020","journal-title":"Dis. Model. Mech."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1159\/000097303","article-title":"The fly as a model for neurodegenerative diseases: Is it worth the jump?","volume":"3","author":"Cauchi","year":"2006","journal-title":"Neurodegener. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"713963","DOI":"10.3389\/fphar.2021.713963","article-title":"Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Surguchov, A. (2021). Invertebrate Models Untangle the Mechanism of Neurodegeneration in Parkinson\u2019s Disease. Cells, 10.","DOI":"10.3390\/cells10020407"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"165614","DOI":"10.1016\/j.bbadis.2019.165614","article-title":"The contribution of multicellular model organisms to neuronal ceroid lipofuscinosis research","volume":"1866","author":"Huber","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/1751-7915.13692","article-title":"Dictyostelium discoideum as a non-mammalian biomedical model","volume":"14","author":"Lacal","year":"2021","journal-title":"Microb. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1387\/ijdb.190256am","article-title":"Actin assembly states in Dictyostelium discoideum at different stages of development and during cellular stress","volume":"63","year":"2019","journal-title":"Int. J. Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.molmed.2006.07.003","article-title":"Towards a molecular understanding of human diseases using Dictyostelium discoideum","volume":"12","author":"Williams","year":"2006","journal-title":"Trends Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature03481","article-title":"The genome of the social amoeba Dictyostelium discoideum","volume":"435","author":"Eichinger","year":"2005","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fernando, S., Allan, C.Y., Mroczek, K., Pearce, X., Sanislav, O., Fisher, P.R., and Annesley, S.J. (2020). Cytotoxicity and Mitochondrial Dysregulation Caused by alpha-Synuclein in Dictyostelium discoideum. Cells, 9.","DOI":"10.3390\/cells9102289"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.3389\/fcell.2021.741662","article-title":"Interactions and Cytotoxicity of Human Neurodegeneration-Associated Proteins Tau and \u03b1-Synuclein in the Simple Model Dictyostelium discoideum","volume":"9","author":"Mroczek","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1242\/dmm.004457","article-title":"Dictyostelium possesses highly diverged presenilin\/gamma-secretase that regulates growth and cell-fate specification and can accurately process human APP: A system for functional studies of the presenilin\/gamma-secretase complex","volume":"3","author":"McMains","year":"2010","journal-title":"Dis. Model. Mech."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1387\/ijdb.190233pf","article-title":"The Dictyostelium model for mitochondrial biology and disease","volume":"63","author":"Pearce","year":"2019","journal-title":"Int. J. Dev. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Smith, P.K., Sen, M.G., Fisher, P.R., and Annesley, S.J. (2019). Modelling of Neuronal Ceroid Lipofuscinosis Type 2 in Dictyostelium discoideum Suggests That Cytopathological Outcomes Result from Altered TOR Signalling. Cells, 8.","DOI":"10.3390\/cells8050469"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11010-009-0111-8","article-title":"Dictyostelium discoideum--a model for many reasons","volume":"329","author":"Annesley","year":"2009","journal-title":"Mol. Cell. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"dmm035600","DOI":"10.1242\/dmm.035600","article-title":"Diacylglycerol kinase (DGKA) regulates the effect of the epilepsy and bipolar disorder treatment valproic acid in Dictyostelium discoideum","volume":"11","author":"Kelly","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1242\/dmm.001271","article-title":"The mood stabiliser lithium suppresses PIP3 signalling in Dictyostelium and human cells","volume":"2","author":"King","year":"2009","journal-title":"Dis. Model. Mech."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1242\/dmm.008029","article-title":"The antiepileptic drug valproic acid and other medium-chain fatty acids acutely reduce phosphoinositide levels independently of inositol in Dictyostelium","volume":"5","author":"Chang","year":"2012","journal-title":"Dis. Model. Mech."},{"key":"ref_22","unstructured":"Alzheimer\u2019s Association (2020). Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 16, 391\u2013460."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jalz.2018.06.3063","article-title":"Racial and ethnic estimates of Alzheimer\u2019s disease and related dementias in the United States (2015-2060) in adults aged >\/=65 years","volume":"15","author":"Matthews","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Trejo-Lopez, J.A., Yachnis, A.T., and Prokop, S. (2021). Neuropathology of Alzheimer\u2019s Disease. Neurotherapeutics, 1\u201313.","DOI":"10.1007\/s13311-021-01146-y"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2174\/156720510790274428","article-title":"Familial Alzheimer\u2019s disease mutations in presenilin 1 do not alter levels of the secreted amyloid-beta protein precursor generated by beta-secretase cleavage","volume":"7","author":"Zhang","year":"2010","journal-title":"Curr. Alzheimer\u2019s Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"335","DOI":"10.2174\/0929867325666180430150940","article-title":"Drugs for Targeted Therapies of Alzheimer\u2019s Disease","volume":"26","author":"Tam","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_27","first-page":"1576","article-title":"An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba Dictyostelium discoideum","volume":"127","author":"Ludtmann","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1080\/15548627.2019.1586245","article-title":"Gamma secretase orthologs are required for lysosomal activity and autophagic degradation in Dictyostelium discoideum, independent of PSEN (presenilin) proteolytic function","volume":"15","author":"Sharma","year":"2019","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.3233\/JAD-150940","article-title":"Non-Catalytic Roles of Presenilin Throughout Evolution","volume":"52","author":"Otto","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/BF03401652","article-title":"The Alzheimer\u2019s disease-associated presenilins are differentially phosphorylated proteins located predominantly within the endoplasmic reticulum","volume":"2","author":"Walter","year":"1996","journal-title":"Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1096\/fj.05-5531fje","article-title":"Presenilin\/gamma-secretase activity regulates protein clearance from the endocytic recycling compartment","volume":"20","author":"Zhang","year":"2006","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12097","DOI":"10.1523\/JNEUROSCI.2635-08.2008","article-title":"Loss of gamma-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis","volume":"28","author":"Tamboli","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.cell.2010.05.008","article-title":"Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations","volume":"141","author":"Lee","year":"2010","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40035-017-0099-z","article-title":"Current understanding of the molecular mechanisms in Parkinson\u2019s disease: Targets for potential treatments","volume":"6","author":"Maiti","year":"2017","journal-title":"Transl. Neurodegener."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"591183","DOI":"10.3389\/fnagi.2020.591183","article-title":"Profiling Non-motor Symptoms in Monogenic Parkinson\u2019s Disease","volume":"12","author":"Liu","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s00441-018-2854-6","article-title":"Is Lewy pathology in the human nervous system chiefly an indicator of neuronal protection or of toxicity?","volume":"373","author":"Chartier","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.tins.2018.11.001","article-title":"Synaptic, Mitochondrial, and Lysosomal Dysfunction in Parkinson\u2019s Disease","volume":"42","author":"Nguyen","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1128\/EC.00366-09","article-title":"Characterization of the Roco protein family in Dictyostelium discoideum","volume":"9","year":"2010","journal-title":"Eukaryot. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1091\/mbc.e10-12-0937","article-title":"The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and controls the actin cytoskeleton","volume":"22","author":"Kicka","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1091\/mbc.e02-06-0335","article-title":"The identification of pats1, a novel gene locus required for cytokinesis in Dictyostelium discoideum","volume":"14","author":"Abysalh","year":"2003","journal-title":"Mol. Biol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.1093\/nar\/gng095","article-title":"Rapid generation of gene disruption constructs by in vitro transposition and identification of a Dictyostelium protein kinase that regulates its rate of growth and development","volume":"31","author":"Abe","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10322","DOI":"10.1073\/pnas.1203223109","article-title":"Roco kinase structures give insights into the mechanism of Parkinson disease-related leucine-rich-repeat kinase 2 mutations","volume":"109","author":"Gilsbach","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"734554","DOI":"10.3389\/fcell.2021.734554","article-title":"A Conserved Role for LRRK2 and Roco Proteins in the Regulation of Mitochondrial Activity","volume":"9","author":"Rosenbusch","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, S., Sanislav, O., Annesley, S.J., and Fisher, P.R. (2018). Mitochondrial HTRA2 Plays a Positive, Protective Role in Dictyostelium discoideum but Is Cytotoxic When Overexpressed. Genes, 9.","DOI":"10.3390\/genes9070355"},{"key":"ref_45","first-page":"1261","article-title":"The Parkinson\u2019s disease-associated protein DJ-1 plays a positive nonmitochondrial role in endocytosis in Dictyostelium cells","volume":"10","author":"Chen","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chen, S., Annesley, S.J., Jasim, R.A.F., and Fisher, P.R. (2021). The Parkinson\u2019s Disease-Associated Protein DJ-1 Protects Dictyostelium Cells from AMPK-Dependent Outcomes of Oxidative Stress. Cells, 10.","DOI":"10.3390\/cells10081874"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S1474-4422(19)30287-X","article-title":"The genetic architecture of Parkinson\u2019s disease","volume":"19","author":"Blauwendraat","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6749","DOI":"10.1073\/pnas.102167299","article-title":"Identification of four candidate cGMP targets in Dictyostelium","volume":"99","author":"Goldberg","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41582-019-0301-2","article-title":"LRRK2 in Parkinson disease: Challenges of clinical trials","volume":"16","author":"Tolosa","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/978-1-62703-302-2_19","article-title":"Mitochondrial respiratory complex function and the phenotypic consequences of dysfunction","volume":"983","author":"Annesley","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1091\/mbc.e06-09-0881","article-title":"Diverse cytopathologies in mitochondrial disease are caused by AMP-activated protein kinase signaling","volume":"18","author":"Bokko","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s12264-017-0196-0","article-title":"Familial Parkinson\u2019s Disease-Associated L166P Mutant DJ-1 is Cleaved by Mitochondrial Serine Protease Omi\/HtrA2","volume":"33","author":"Fu","year":"2017","journal-title":"Neurosci. Bull."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/ncb1644","article-title":"The mitochondrial protease HtrA2 is regulated by Parkinson\u2019s disease-associated kinase PINK1","volume":"9","author":"Klupsch","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/cdd.2011.90","article-title":"Phosphorylation of HtrA2 by cyclin-dependent kinase-5 is important for mitochondrial function","volume":"19","author":"Fitzgerald","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2025022118","DOI":"10.1073\/pnas.2025022118","article-title":"Oligomeric assembly regulating mitochondrial HtrA2 function as examined by methyl-TROSY NMR","volume":"118","author":"Toyama","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1007\/s00415-010-5485-8","article-title":"Mutation analysis of Parkin, PINK1 and DJ-1 genes in Chinese patients with sporadic early onset parkinsonism","volume":"257","author":"Guo","year":"2010","journal-title":"J. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Repici, M., and Giorgini, F. (2019). DJ-1 in Parkinson\u2019s Disease: Clinical Insights and Therapeutic Perspectives. J. Clin. Med., 8.","DOI":"10.3390\/jcm8091377"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Mencke, P., Boussaad, I., Romano, C.D., Kitami, T., Linster, C.L., and Kruger, R. (2021). The Role of DJ-1 in Cellular Metabolism and Pathophysiological Implications for Parkinson\u2019s Disease. Cells, 10.","DOI":"10.3390\/cells10020347"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1111\/ejn.12872","article-title":"Evidence for a common biological pathway linking three Parkinson\u2019s disease-causing genes: Parkin, PINK1 and DJ-1","volume":"41","author":"Christoffels","year":"2015","journal-title":"Eur. J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/s42003-019-0644-7","article-title":"Partially oxidized DJ-1 inhibits alpha-synuclein nucleation and remodels mature alpha-synuclein fibrils in vitro","volume":"2","author":"Kumar","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1111\/gtc.12382","article-title":"Unexpected mitochondrial matrix localization of Parkinson\u2019s disease-related DJ-1 mutants but not wild-type DJ-1","volume":"21","author":"Kojima","year":"2016","journal-title":"Genes Cells"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1073\/pnas.1708754115","article-title":"DJ-1 deficiency impairs synaptic vesicle endocytosis and reavailability at nerve terminals","volume":"115","author":"Kyung","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4805","DOI":"10.1093\/hmg\/ddt332","article-title":"DJ-1 associates with lipid rafts by palmitoylation and regulates lipid rafts-dependent endocytosis in astrocytes","volume":"22","author":"Kim","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1387\/ijdb.190236jk","article-title":"The endocytic pathways of Dictyostelium discoideum","volume":"63","author":"Vines","year":"2019","journal-title":"Int. J. Dev. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1242\/dmm.025684","article-title":"Immortalized Parkinson\u2019s disease lymphocytes have enhanced mitochondrial respiratory activity","volume":"9","author":"Annesley","year":"2016","journal-title":"Dis. Model. Mech."},{"key":"ref_66","first-page":"1819209","article-title":"Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson\u2019s Disease Patients","volume":"2016","author":"Haylett","year":"2016","journal-title":"Parkinsons Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"dmm040899","DOI":"10.1242\/dmm.040899","article-title":"Misfolded alpha-synuclein causes hyperactive respiration without functional deficit in live neuroblastoma cells","volume":"13","author":"Ugalde","year":"2020","journal-title":"Dis. Model. Mech."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1242\/dmm.003319","article-title":"Legionella pneumophila multiplication is enhanced by chronic AMPK signalling in mitochondrially diseased Dictyostelium cells","volume":"2","author":"Francione","year":"2009","journal-title":"Dis. Model. Mech."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/jnc.14955","article-title":"A simple, versatile and robust centrifugation-based filtration protocol for the isolation and quantification of alpha-synuclein monomers, oligomers and fibrils: Towards improving experimental reproducibility in alpha-synuclein research","volume":"153","author":"Kumar","year":"2020","journal-title":"J. NeuroChem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1097\/WAD.0b013e31823899cc","article-title":"Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson Disease, dementia with Lewy bodies, multiple system atrophy) from Alzheimer disease","volume":"26","author":"Tateno","year":"2012","journal-title":"Alzheimers Dis. Assoc. Disord."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"10224","DOI":"10.1074\/jbc.REV120.011743","article-title":"The emerging role of alpha-synuclein truncation in aggregation and disease","volume":"295","author":"Sorrentino","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_72","first-page":"17","article-title":"Novel subcellular localization for \u03b1-synuclein: Possible functional consequences","volume":"9","author":"Schon","year":"2015","journal-title":"Front. Neuroanat."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0888-7543(90)90297-8","article-title":"Batten disease (Spielmeyer-Vogt disease, juvenile onset neuronal ceroid-lipofuscinosis) gene (CLN3) maps to human chromosome 16","volume":"8","author":"Gardiner","year":"1990","journal-title":"Genomics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1016\/j.bpj.2010.06.035","article-title":"The N-terminus of the intrinsically disordered protein alpha-synuclein triggers membrane binding and helix folding","volume":"99","author":"Bartels","year":"2010","journal-title":"Biophys. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1016\/S0021-9258(17)42989-9","article-title":"Phosphorylation affects the ability of tau protein to promote microtubule assembly","volume":"259","author":"Lindwall","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e224","DOI":"10.1038\/emm.2016.16","article-title":"AMPK activators: Mechanisms of action and physiological activities","volume":"48","author":"Kim","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3389\/fnins.2020.00082","article-title":"Cortical and Striatal Circuits in Huntington\u2019s Disease","volume":"14","author":"Blumenstock","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nrn1806","article-title":"Normal huntingtin function: An alternative approach to Huntington\u2019s disease","volume":"6","author":"Cattaneo","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Myre, M.A., Lumsden, A.L., Thompson, M.N., Wasco, W., MacDonald, M.E., and Gusella, J.F. (2011). Deficiency of huntingtin has pleiotropic effects in the social amoeba Dictyostelium discoideum. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002052"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"25571","DOI":"10.1074\/jbc.M115.676247","article-title":"The Social Amoeba Dictyostelium discoideum Is Highly Resistant to Polyglutamine Aggregation","volume":"290","author":"Santarriaga","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"18858","DOI":"10.1002\/jcp.28524","article-title":"Deletion of Htt cause alterations in cAMP signaling and spatial patterning in Dictyostelium discoideum","volume":"234","author":"Bhadoriya","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1423-0127-19-41","article-title":"Clues to gamma-secretase, huntingtin and Hirano body normal function using the model organism Dictyostelium discoideum","volume":"19","author":"Myre","year":"2012","journal-title":"J. Biomed. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/ng1095-155","article-title":"Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington\u2019s disease gene homologue","volume":"11","author":"Zeitlin","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3233\/JHD-140112","article-title":"Huntingtin Supplies a csaA-Independent Function Essential for EDTA-Resistant Homotypic Cell Adhesion in Dictyostelium discoideum","volume":"3","author":"Thompson","year":"2014","journal-title":"J. Huntingt. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1091\/mbc.e10-11-0926","article-title":"Dictyostelium huntingtin controls chemotaxis and cytokinesis through the regulation of myosin II phosphorylation","volume":"22","author":"Wang","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/s41582-019-0138-8","article-title":"Therapeutic landscape for Batten disease: Current treatments and future prospects","volume":"15","author":"Johnson","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Mole, S.E., Schulz, A., and Haltia, M. (2020). The neuronal ceroid-lipofuscinoses (batten disease). Rosenberg\u2019s Molecular and Genetic Basis of Neurological and Psychiatric Disease, Elsevier.","DOI":"10.1016\/B978-0-12-813866-3.00004-7"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s40263-019-00620-8","article-title":"Current and Emerging Treatment Strategies for Neuronal Ceroid Lipofuscinoses","volume":"33","author":"Kohlschutter","year":"2019","journal-title":"CNS Drugs"},{"key":"ref_89","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_90","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1016\/j.bbadis.2015.04.027","article-title":"Cell biology of the NCL proteins: What they do and don\u2019t do","volume":"1852","author":"Kovacs","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12929-016-0301-0","article-title":"Using the social amoeba Dictyostelium to study the functions of proteins linked to neuronal ceroid lipofuscinosis","volume":"23","author":"Huber","year":"2016","journal-title":"J. Biomed. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Huber, R.J., Myre, M.A., and Cotman, S.L. (2014). Loss of Cln3 function in the social amoeba Dictyostelium discoideum causes pleiotropic effects that are rescued by human CLN3. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110544"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1002\/pmic.200900516","article-title":"The secreted proteome profile of developing Dictyostelium discoideum cells","volume":"10","author":"Bakthavatsalam","year":"2010","journal-title":"Proteomics"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/pmic.201100313","article-title":"Investigating the macropinocytic proteome of Dictyostelium amoebae by high-resolution mass spectrometry","volume":"12","author":"Journet","year":"2012","journal-title":"Proteomics"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2164-9-291","article-title":"Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium","volume":"9","author":"Sillo","year":"2008","journal-title":"BMC Genom."},{"key":"ref_96","first-page":"147","article-title":"Partial genetic suppression of a loss-of-function mutant of the neuronal ceroid lipofuscinosis-associated protease TPP1 in Dictyostelium discoideum","volume":"8","author":"Phillips","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"ref_97","first-page":"1","article-title":"Molecular networking in the neuronal ceroid lipofuscinoses: Insights from mammalian models and the social amoeba Dictyostelium discoideum","volume":"27","author":"Huber","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"ref_98","first-page":"897","article-title":"A tripeptidyl peptidase 1 is a binding partner of the Golgi pH regulator (GPHR) in Dictyostelium","volume":"10","author":"Stumpf","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"ref_99","first-page":"1","article-title":"Dictyostelium transcriptional responses to Pseudomonas aeruginosa: Common and specific effects from PAO1 and PA14 strains","volume":"8","author":"Bloomfield","year":"2008","journal-title":"BMC Microbiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1016\/j.bbadis.2018.08.013","article-title":"Cln3 function is linked to osmoregulation in a Dictyostelium model of Batten disease","volume":"1864","author":"Mathavarajah","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.cellsig.2017.11.001","article-title":"Cln5 is secreted and functions as a glycoside hydrolase in Dictyostelium","volume":"42","author":"Huber","year":"2018","journal-title":"Cell. Signal."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cellsig.2019.02.004","article-title":"Comparative transcriptomics reveals mechanisms underlying cln3-deficiency phenotypes in Dictyostelium","volume":"58","author":"Huber","year":"2019","journal-title":"Cell. Signal."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cellsig.2017.03.022","article-title":"Loss of Cln3 impacts protein secretion in the social amoeba Dictyostelium","volume":"35","author":"Huber","year":"2017","journal-title":"Cell. Signal."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/19336918.2016.1236179","article-title":"Aberrant adhesion impacts early development in a Dictyostelium model for juvenile neuronal ceroid lipofuscinosis","volume":"11","author":"Huber","year":"2017","journal-title":"Cell Adhes. Migr."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1074\/mcp.M600113-MCP200","article-title":"Proteomics Fingerprinting of Phagosome Maturation and Evidence for the Role of a G\u03b1 during Uptake* S","volume":"5","author":"Gotthardt","year":"2006","journal-title":"Mol. Cell. Proteom."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1021\/pr050350q","article-title":"Identification of Novel Centrosomal Proteins in Dictyostelium d iscoideum by Comparative Proteomic Approaches","volume":"5","author":"Reinders","year":"2006","journal-title":"J. Proteome Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.bbamcr.2018.07.017","article-title":"Secretion and function of Cln5 during the early stages of Dictyostelium development","volume":"1865","author":"Huber","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"109572","DOI":"10.1016\/j.cellsig.2020.109572","article-title":"Mfsd8 localizes to endocytic compartments and influences the secretion of Cln5 and cathepsin D in Dictyostelium","volume":"70","author":"Huber","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3833","DOI":"10.1242\/jcs.112.21.3833","article-title":"Characterization of Dictyostelium discoideum cathepsin D","volume":"112","author":"Journet","year":"1999","journal-title":"J. Cell Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1111\/j.1462-5822.2007.00993.x","article-title":"Flotillin and RacH modulate the intracellular immunity of Dictyostelium to Mycobacterium marinum infection","volume":"9","author":"Hagedorn","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1091\/mbc.01-09-0454","article-title":"Dictyostelium LvsB mutants model the lysosomal defects associated with Chediak-Higashi syndrome","volume":"13","author":"Harris","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"ref_112","first-page":"80","article-title":"Staurosporine induced poly (ADP-ribose) polymerase independent cell death in Dictyostelium discoideum","volume":"50","author":"Mir","year":"2012","journal-title":"Indian J. Exp. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1111\/j.1462-5822.2011.01662.x","article-title":"Salmonella typhimurium is pathogenic for Dictyostelium cells and subverts the starvation response","volume":"13","author":"Sillo","year":"2011","journal-title":"Cell. Microbiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/j.1462-5822.2010.01532.x","article-title":"Role of magnesium and a phagosomal P-type ATPase in intracellular bacterial killing","volume":"13","author":"Lelong","year":"2011","journal-title":"Cell. Microbiol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Le Coadic, M., Froquet, R., Lima, W.C., Dias, M., Marchetti, A., and Cosson, P. (2013). Phg1\/TM9 proteins control intracellular killing of bacteria by determining cellular levels of the Kil1 sulfotransferase in Dictyostelium. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053259"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1242\/jcs.108.10.3331","article-title":"Identification of major proteins associated with Dictyostelium discoideum endocytic vesicles","volume":"108","author":"Adessi","year":"1995","journal-title":"J. Cell Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/1471-2164-8-123","article-title":"STATc is a key regulator of the transcriptional response to hyperosmotic shock","volume":"8","author":"Na","year":"2007","journal-title":"BMC Genom."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1073\/pnas.080508097","article-title":"The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis","volume":"97","author":"Bellizzi","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1080\/09687680802629329","article-title":"Protein acyl thioesterases (Review)","volume":"26","author":"Zeidman","year":"2009","journal-title":"Mol. Membr. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1002\/jimd.12106","article-title":"Cln3-mutations underlying juvenile neuronal ceroid lipofuscinosis cause significantly reduced levels of Palmitoyl-protein thioesterases-1 (Ppt1)-protein and Ppt1-enzyme activity in the lysosome","volume":"42","author":"Appu","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"49","DOI":"10.4103\/1817-1745.111424","article-title":"Novel CLN1 mutation with atypical juvenile neuronal ceroid lipofuscinosis","volume":"8","author":"Khan","year":"2013","journal-title":"J. Pediatr. Neurosci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1042\/bj3570049","article-title":"Production and characterization of recombinant human CLN2 protein for enzyme-replacement therapy in late infantile neuronal ceroid lipofuscinosis","volume":"357","author":"Lin","year":"2001","journal-title":"BioChem. J."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"102323","DOI":"10.1016\/j.scr.2021.102323","article-title":"Generation of pathogenic TPP1 mutations in human stem cells as a model for neuronal ceroid lipofuscinosis type 2 disease","volume":"53","author":"Ma","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ejpn.2021.05.015","article-title":"Unraveling neuronal ceroid lipofuscinosis type 2 (CLN2) disease: A tertiary center experience for determinants of diagnostic delay","volume":"33","author":"Ardicli","year":"2021","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/S1071-9091(96)80031-3","article-title":"The neuronal ceroid-lipofuscinoses","volume":"3","author":"Goebel","year":"1996","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.exer.2016.03.023","article-title":"Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease","volume":"146","author":"Whiting","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2147\/TCRM.S241048","article-title":"Changing Times for CLN2 Disease: The Era of Enzyme Replacement Therapy","volume":"16","author":"Specchio","year":"2020","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3976","DOI":"10.1074\/jbc.M806947200","article-title":"Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis","volume":"284","author":"Pal","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1074\/jbc.M008562200","article-title":"The human CLN2 protein\/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH","volume":"276","author":"Lin","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0167-4838(98)00012-0","article-title":"Purification and characterisation of a tripeptidyl aminopeptidase I from rat spleen","volume":"1384","author":"Vines","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.seizure.2018.08.027","article-title":"Homozygous missense TPP1 mutation associated with mild late infantile neuronal ceroid lipofuscinosis and the genotype-phenotype correlation","volume":"69","author":"Chen","year":"2019","journal-title":"Seizure"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/ajmg.1320420428","article-title":"Mitochondrial ATP synthase subunit c storage in the ceroid-lipofuscinoses (Batten disease)","volume":"42","author":"Palmer","year":"1992","journal-title":"Am. J. Med. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1515\/BC.2006.135","article-title":"Tripeptidyl-peptidase I in health and disease","volume":"387","author":"Golabek","year":"2006","journal-title":"Biol. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1042\/EBC20170055","article-title":"Dysregulation of autophagy as a common mechanism in lysosomal storage diseases","volume":"61","author":"Seranova","year":"2017","journal-title":"Essays BioChem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1128\/EC.00208-14","article-title":"The Dictyostelium discoideum GPHR ortholog is an endoplasmic reticulum and Golgi protein with roles during development","volume":"14","author":"Deckstein","year":"2015","journal-title":"Eukaryot. Cell"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/ana.410420517","article-title":"Clinical and magnetic resonance imaging findings in batten disease: Analysis of the major mutation (1.02-Kb Deletion)","volume":"42","author":"Autti","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/j.1468-1331.2007.01692.x","article-title":"Thalami and corona radiata in juvenile NCL (CLN3): A voxel-based morphometric study","volume":"14","author":"Autti","year":"2007","journal-title":"Eur. J. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/jnr.20367","article-title":"CLN3, the protein associated with batten disease: Structure, function and localization","volume":"79","author":"Phillips","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"14361","DOI":"10.1074\/jbc.M114.621706","article-title":"Unbiased cell-based screening in a neuronal cell model of Batten disease highlights an interaction between Ca2+ homeostasis, autophagy, and CLN3 protein function","volume":"290","author":"Chandrachud","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1046\/j.1471-4159.1996.67020677.x","article-title":"Apoptosis as the mechanism of neurodegeneration in Batten\u2019s disease","volume":"67","author":"Lane","year":"1996","journal-title":"J. NeuroChem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1093\/hmg\/ddh321","article-title":"Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to defects in the endocytic pathway","volume":"13","author":"Luiro","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.biopha.2013.12.010","article-title":"Effect of CLN3 silencing by RNA interference on the proliferation and apoptosis of human colorectal cancer cells","volume":"68","author":"Zhu","year":"2014","journal-title":"Biomed. Pharmacother."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1093\/jnen\/nlab064","article-title":"An Unusual Presentation of CLN3-Associated Batten Disease With Classic Histopathologic and Ultrastructural Findings","volume":"80","author":"Evans","year":"2021","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"C1388","DOI":"10.1152\/ajpcell.00272.2009","article-title":"Osmoregulation of ceroid neuronal lipofuscinosis type 3 in the renal medulla","volume":"298","author":"Stein","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"9592","DOI":"10.1074\/jbc.RA119.008852","article-title":"Lysosomal proteome analysis reveals that CLN3-defective cells have multiple enzyme deficiencies associated with changes in intracellular trafficking","volume":"294","author":"Schmidtke","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ajhg.2011.07.003","article-title":"Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis","volume":"89","author":"Noskova","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/cge.12020","article-title":"Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease","volume":"83","author":"Andermann","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Benitez, B.A., Alvarado, D., Cai, Y., Mayo, K., Chakraverty, S., Norton, J., Morris, J.C., Sands, M.S., Goate, A., and Cruchaga, C. (2011). Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal ceroid-lipofuscinosis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026741"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3389\/fncel.2014.00116","article-title":"CSPalpha-chaperoning presynaptic proteins","volume":"8","author":"Donnelier","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.1111\/febs.14936","article-title":"DNAJC proteins and pathways to parkinsonism","volume":"286","author":"Roosen","year":"2019","journal-title":"FEBS J."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/975","article-title":"CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis","volume":"19","author":"Savukoski","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Moharir, A., Peck, S.H., Budden, T., and Lee, S.Y. (2013). The role of N-glycosylation in folding, trafficking, and functionality of lysosomal protein CLN5. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074299"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"657406","DOI":"10.3389\/fcell.2021.657406","article-title":"Aberrant Autophagy Impacts Growth and Multicellular Development in a Dictyostelium Knockout Model of CLN5 Disease","volume":"9","author":"McLaren","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"E530","DOI":"10.1002\/humu.20975","article-title":"Mutations in MFSD8\/CLN7 are a frequent cause of variant-late infantile neuronal ceroid lipofuscinosis","volume":"30","author":"Aiello","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1111\/j.1600-0854.2010.01073.x","article-title":"Lysosomal targeting of the CLN7 membrane glycoprotein and transport via the plasma membrane require a dileucine motif","volume":"11","author":"Steenhuis","year":"2010","journal-title":"Traffic"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1086\/518902","article-title":"The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter","volume":"81","author":"Siintola","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.neulet.2007.12.026","article-title":"Short arm of chromosome 11 and sporadic Alzheimer\u2019s disease: Catalase and cathepsin D gene polymorphisms","volume":"432","author":"Capurso","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/j.bbadis.2013.04.008","article-title":"NCL diseases\u2014Clinical perspectives","volume":"1832","author":"Schulz","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s00401-008-0426-7","article-title":"Novel mutation and the first prenatal screening of cathepsin D deficiency (CLN10)","volume":"117","author":"Fritchie","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1093\/brain\/awl107","article-title":"Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis","volume":"129","author":"Siintola","year":"2006","journal-title":"Brain"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.molmed.2020.07.004","article-title":"Pro-cathepsin D, Prosaposin, and Progranulin: Lysosomal Networks in Parkinsonism","volume":"26","author":"Tayebi","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1093\/brain\/awaa414","article-title":"Early-onset phenotype of bi-allelic GRN mutations","volume":"144","author":"Neuray","year":"2021","journal-title":"Brain"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"135394","DOI":"10.1016\/j.neulet.2020.135394","article-title":"Regulation of progranulin expression and location by sortilin in oxygen-glucose deprivation\/reoxygenation injury","volume":"738","author":"Wang","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.parkreldis.2021.03.020","article-title":"A novel homozygous mutation in ATP13A2 gene causing pure hereditary spastic paraplegia","volume":"86","author":"Ban","year":"2021","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s12098-019-03167-0","article-title":"Kufor-Rakeb Syndrome\/Parkinson Disease Type 9","volume":"87","author":"Gowda","year":"2020","journal-title":"Indian J. Pediatr."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1002\/jnr.23112","article-title":"Characterization of cellular protective effects of ATP13A2\/PARK9 expression and alterations resulting from pathogenic mutants","volume":"90","author":"Covy","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1093\/hmg\/dds558","article-title":"Cathepsin F mutations cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis","volume":"22","author":"Smith","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ajhg.2012.05.023","article-title":"A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the ubiquitin-proteasome system","volume":"91","author":"Staropoli","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s12035-011-8194-0","article-title":"Progressive myoclonic epilepsy-associated gene KCTD7 is a regulator of potassium conductance in neurons","volume":"44","author":"Azizieh","year":"2011","journal-title":"Mol. Neurobiol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.tins.2007.12.004","article-title":"Abnormal development of the human cerebral cortex: Genetics, functional consequences and treatment options","volume":"31","author":"Guerrini","year":"2008","journal-title":"Trends Neurosci."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1159\/000110270","article-title":"Epidemiology of lissencephaly type I","volume":"10","author":"Arts","year":"1991","journal-title":"Neuroepidemiology"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1177\/08830738050200040701","article-title":"Genotype-phenotype correlation in lissencephaly and subcortical band heterotopia: The key questions answered","volume":"20","author":"Leventer","year":"2005","journal-title":"J. Child. Neurol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0035-3787(07)90460-9","article-title":"Genetic and clinical aspects of lissencephaly","volume":"163","author":"Verloes","year":"2007","journal-title":"Rev. Neurol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S1357-4310(00)01730-5","article-title":"Lissencephaly and subcortical band heterotopia: Molecular basis and diagnosis","volume":"6","author":"Leventer","year":"2000","journal-title":"Mol. Med. Today"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s41556-020-0501-4","article-title":"Lis1 activates dynein motility by modulating its pairing with dynactin","volume":"22","author":"Elshenawy","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.nbd.2009.02.008","article-title":"Neuronal migration disorders","volume":"38","author":"Guerrini","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.semcdb.2010.10.007","article-title":"Functional analyses of lissencephaly-related proteins in Dictyostelium","volume":"22","author":"Meyer","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1091\/mbc.e05-01-0069","article-title":"Dictyostelium LIS1 is a centrosomal protein required for microtubule\/cell cortex interactions, nucleus\/centrosome linkage, and actin dynamics","volume":"16","author":"Rehberg","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1387\/ijdb.190228rw","article-title":"Dictyostelium discoideum as a pharmacological model system to study the mechanisms of medicinal drugs and natural products","volume":"63","author":"Schaf","year":"2019","journal-title":"Int. J. Dev. Biol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"721630","DOI":"10.3389\/fcell.2021.721630","article-title":"CRISPR Toolbox for Genome Editing in Dictyostelium","volume":"9","author":"Yamashita","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrg2484","article-title":"RNA-Seq: A revolutionary tool for transcriptomics","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"8803","DOI":"10.1073\/pnas.89.18.8803","article-title":"Tagging developmental genes in Dictyostelium by restriction enzyme-mediated integration of plasmid DNA","volume":"89","author":"Kuspa","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12915-021-01108-y","article-title":"Mutant resources for functional genomics in Dictyostelium discoideum using REMI-seq technology","volume":"19","author":"Gruenheit","year":"2021","journal-title":"BMC Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1101\/gr.209932.116","article-title":"A better way to discover gene function in the social amoeba Dictyostelium discoideum","volume":"26","author":"Loomis","year":"2016","journal-title":"Genome Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/bph.14892","article-title":"A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models","volume":"177","author":"Perry","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1111\/bph.15351","article-title":"Phytocannabinoid-dependent mTORC1 regulation is dependent upon inositol polyphosphate multikinase activity","volume":"178","author":"Warren","year":"2021","journal-title":"Br. J. Pharm."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1111\/bph.12443","article-title":"Naringenin inhibits the growth of Dictyostelium and MDCK-derived cysts in a TRPP2 (polycystin-2)-dependent manner","volume":"171","author":"Waheed","year":"2014","journal-title":"Br. J. Pharm."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"dmm032375","DOI":"10.1242\/dmm.032375","article-title":"Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum","volume":"11","author":"Cocorocchio","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"23617","DOI":"10.1073\/pnas.2008980117","article-title":"Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling","volume":"117","author":"Warren","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1093\/emboj\/18.10.2734","article-title":"Loss of a prolyl oligopeptidase confers resistance to lithium by elevation of inositol (1,4,5) trisphosphate","volume":"18","author":"Williams","year":"1999","journal-title":"EMBO J."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/417292a","article-title":"A common mechanism of action for three mood-stabilizing drugs","volume":"417","author":"Williams","year":"2002","journal-title":"Nature"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.nbd.2013.10.017","article-title":"Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid","volume":"62","author":"Chang","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1124\/jpet.114.218768","article-title":"Seizure control by derivatives of medium chain fatty acids associated with the ketogenic diet show novel branching-point structure for enhanced potency","volume":"352","author":"Chang","year":"2015","journal-title":"J. Pharm. Exp."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.neuropharm.2012.11.004","article-title":"Seizure control by ketogenic diet-associated medium chain fatty acids","volume":"69","author":"Chang","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"fcab160","DOI":"10.1093\/braincomms\/fcab160","article-title":"Vita: A feasibility study of a blend of medium chain triglycerides to manage drug-resistant epilepsy","volume":"3","author":"Schoeler","year":"2021","journal-title":"Brain Commun."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3389\/fncel.2018.00199","article-title":"All You Need Is Fats-for Seizure Control: Using Amoeba to Advance Epilepsy Research","volume":"12","author":"Warren","year":"2018","journal-title":"Front. Cell. Neurosci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/3\/463\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:10:27Z","timestamp":1760134227000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/3\/463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":196,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cells11030463"],"URL":"https:\/\/doi.org\/10.3390\/cells11030463","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]}}}