{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T03:12:41Z","timestamp":1785640361468,"version":"3.56.0"},"reference-count":107,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["RO1NS047663"],"award-info":[{"award-number":["RO1NS047663"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Patatin-like phospholipase domain-containing protein 6 (PNPLA6), originally called Neuropathy Target Esterase (NTE), belongs to a family of hydrolases with at least eight members in mammals. PNPLA6\/NTE was first identified as a key factor in Organophosphate-induced delayed neuropathy, a degenerative syndrome that occurs after exposure to organophosphates found in pesticides and nerve agents. More recently, mutations in PNPLA6\/NTE have been linked with a number of inherited diseases with diverse clinical symptoms that include spastic paraplegia, ataxia, and chorioretinal dystrophy. A conditional knockout of PNPLA6\/NTE in the mouse brain results in age-related neurodegeneration, whereas a complete knockout causes lethality during embryogenesis due to defects in the development of the placenta. PNPLA6\/NTE is an evolutionarily conserved protein that in Drosophila is called Swiss-Cheese (SWS). Loss of SWS in the fly also leads to locomotory defects and neuronal degeneration that progressively worsen with age. This review will describe the identification of PNPLA6\/NTE, its expression pattern, and normal role in lipid homeostasis, as well as the consequences of altered NPLA6\/NTE function in both model systems and patients.<\/jats:p>","DOI":"10.3390\/metabo12040284","type":"journal-article","created":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T23:31:43Z","timestamp":1648164703000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["PNPLA6\/NTE, an Evolutionary Conserved Phospholipase Linked to a Group of Complex Human Diseases"],"prefix":"10.3390","volume":"12","author":[{"given":"Doris","family":"Kretzschmar","sequence":"first","affiliation":[{"name":"Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7425","DOI":"10.1523\/JNEUROSCI.17-19-07425.1997","article-title":"The swiss cheese mutant causes glial hyperwrapping and brain degeneration in Drosophila","volume":"17","author":"Kretzschmar","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3320001","article-title":"Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man","volume":"332","author":"Lush","year":"1998","journal-title":"Biochem. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"229","DOI":"10.17816\/ecogen16327","article-title":"Human diseases associated with NTE gene","volume":"18","author":"Melentev","year":"2020","journal-title":"Ecol. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1136\/jnnp-2014-307793","article-title":"Ataxia meets chorioretinal dystrophy and hypogonadism: Boucher-Neuhauser syndrome due to PNPLA6 mutations","volume":"86","author":"Synofzik","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0925-4773(99)00239-7","article-title":"Cloning and expression of the murine sws\/NTE gene","volume":"90","author":"Moser","year":"2000","journal-title":"Mech. Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"24024","DOI":"10.1074\/jbc.M400830200","article-title":"Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells","volume":"279","author":"Zaccheo","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11594","DOI":"10.1523\/JNEUROSCI.3007-09.2009","article-title":"Neuropathy target esterase is required for adult vertebrate axon maintenance","volume":"29","author":"Read","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5614","DOI":"10.1038\/ncomms6614","article-title":"Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness","volume":"6","author":"Kmoch","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10885","DOI":"10.1523\/JNEUROSCI.3015-08.2008","article-title":"Swiss Cheese, a protein involved in progressive neurodegeneration, acts as a noncanonical regulatory subunit for PKA-C3","volume":"28","author":"Wentzell","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.2307\/4579816","article-title":"The pharmacological action of certain phenol esters, with special reference to the etiology of so-called ginger paralysis (second report)","volume":"45","author":"Smith","year":"1930","journal-title":"Public Health Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/j.1749-6632.1969.tb15851.x","article-title":"Studies on delayed neurotoxicity produced by some organophosphorus compounds","volume":"160","author":"Aldridge","year":"1969","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13P","DOI":"10.1042\/bj1100013Pa","article-title":"An enzyme in hen brain hydrolysing phenyl phenylacetate: A possible connection with the delayed neurotoxic effect of some organophosphorus compounds","volume":"110","author":"Johnson","year":"1968","journal-title":"Biochem. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1042\/bj1110487","article-title":"A phosphorylation site in brain and the delayed neurotoxic effect of some organophosphorus compounds","volume":"111","author":"Johnson","year":"1969","journal-title":"Biochem. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1042\/bj1200523","article-title":"Organophosphorus and other inhibitors of brain \u2018neurotoxic esterase\u2019 and the development of delayed neurotoxicity in hens","volume":"120","author":"Johnson","year":"1970","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/2221066a0","article-title":"Protection by some Carbamates against the Delayed Neurotoxic Effects of Di-isopropyl Phosphorofluoridate","volume":"222","author":"Johnson","year":"1969","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1042\/bj1770549","article-title":"Rapid aging of neurotoxic esterase after inhibition by di-isopropyl phosphorofluoridate","volume":"177","author":"Clothier","year":"1979","journal-title":"Biochem. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"42","DOI":"10.4103\/JPN.JPN_45_18","article-title":"Organophosphorus-Induced Toxic Myeloneuropathy: Series of Three Adolescent Patients with Short Review","volume":"14","author":"Nayak","year":"2019","journal-title":"J. Pediatr. Neurosci."},{"key":"ref_18","first-page":"527","article-title":"Organophosphorus compounds","volume":"1","author":"Davis","year":"1980","journal-title":"Exp. Clin. Neurotoxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ant.2020.01.001","article-title":"Neuropathy target esterase (NTE\/PNPLA6) and organophosphorus compound-induced delayed neurotoxicity (OPIDN)","volume":"Volume 4","author":"Richardson","year":"2020","journal-title":"Advances in Neurotoxicology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2165\/00139709-200524010-00003","article-title":"Organophosphate-induced delayed polyneuropathy","volume":"24","author":"Lotti","year":"2005","journal-title":"Toxicol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.toxlet.2009.10.032","article-title":"Organophosphorus-induced delayed neuropathy: A simple and efficient therapeutic strategy","volume":"192","author":"Emerick","year":"2010","journal-title":"Toxicol. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cbi.2012.07.002","article-title":"Mechanisms for consideration for intervention in the development of organophosphorus-induced delayed neuropathy","volume":"199","author":"Emerick","year":"2012","journal-title":"Chem. Biol. Interact."},{"key":"ref_23","unstructured":"Gupta, R.C. (2015). Handbook of toxicology of chemical warfare agents, Academic Press."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1136\/jnnp.17.3.163","article-title":"The toxic effects of tri-ortho-cresyl phosphate on the nervous system: An experimental study in hens","volume":"17","author":"Cavanagh","year":"1954","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_25","first-page":"253","article-title":"Organophosphorous neuropathy. II. A fine-structural study of the early stages of axonal degeneration","volume":"94","author":"Bouldin","year":"1979","journal-title":"Am. J. Pathol."},{"key":"ref_26","first-page":"241","article-title":"Organophosphorous neuropathy. I. A teased-fiber study of the spatio-temporal spread of axonal degeneraion","volume":"94","author":"Bouldin","year":"1979","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"110666","DOI":"10.1016\/j.mehy.2021.110666","article-title":"SARM1-mediated wallerian degeneration: A possible mechanism underlying organophosphorus-induced delayed neuropathy","volume":"155","author":"Song","year":"2021","journal-title":"Med. Hypotheses"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"24477","DOI":"10.1074\/jbc.M002921200","article-title":"Membrane association of and critical residues in the catalytic domain of human neuropathy target esterase","volume":"275","author":"Atkins","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8820","DOI":"10.1074\/jbc.M210743200","article-title":"Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in mammalian cells","volume":"278","author":"Li","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10930-006-9058-8","article-title":"Modeling the tertiary structure of the patatin domain of neuropathy target esterase","volume":"26","author":"Wijeyesakere","year":"2007","journal-title":"Protein J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1523\/JNEUROSCI.5097-04.2005","article-title":"Loss of Swiss cheese\/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila","volume":"25","author":"Tschape","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.bbapap.2005.08.024","article-title":"Dynamics of signaling by PKA","volume":"1754","author":"Taylor","year":"2005","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"d580","DOI":"10.2741\/francis","article-title":"Mechanisms of autoinhibition in cyclic nucleotide-dependent protein kinases","volume":"7","author":"Francis","year":"2002","journal-title":"Front Biosci"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wentzell, J.S., Cassar, M., and Kretzschmar, D. (2014). Organophosphate-induced changes in the PKA regulatory function of Swiss Cheese\/NTE lead to behavioral deficits and neurodegeneration. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087526"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.phrs.2010.03.006","article-title":"Regulation of neuropathy target esterase by the cAMP\/protein kinase A signal","volume":"62","author":"Chen","year":"2010","journal-title":"Pharmacol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1194\/jlr.R800082-JLR200","article-title":"Mammalian patatin domain containing proteins: A family with diverse lipolytic activities involved in multiple biological functions","volume":"50 Suppl","author":"Kienesberger","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7983","DOI":"10.1073\/pnas.1232473100","article-title":"Evidence that mouse brain neuropathy target esterase is a lysophospholipase","volume":"100","author":"Quistad","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20942","DOI":"10.1074\/jbc.M200330200","article-title":"Human Neuropathy Target Esterase Catalyzes Hydrolysis of Membrane Lipids","volume":"277","author":"Atkins","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.bbalip.2012.07.023","article-title":"Neuronal phospholipid deacylation is essential for axonal and synaptic integrity","volume":"1831","author":"Glynn","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sandoval, G. (2012). Phospholipases: An Overview. Lipases and Phospholipases: Methods and Protocols, Humana Press.","DOI":"10.1007\/978-1-61779-600-5"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/0006-2952(87)90104-3","article-title":"Neurotoxic esterase: Characterization of the solubilized enzyme and the conditions for its solubilization from chicken brain microsomal membranes with ionic, zwitterionic, or nonionic detergents","volume":"36","author":"Davis","year":"1987","journal-title":"Biochem. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/0041-008X(89)90332-3","article-title":"Modulation of neurotoxic esterase activity in vitro by phospholipids","volume":"97","author":"Pope","year":"1989","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.taap.2008.07.015","article-title":"Cellular function of neuropathy target esterase in lysophosphatidylcholine action","volume":"232","author":"Vose","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/j.bbamem.2010.03.015","article-title":"Influence of lysophospholipid hydrolysis by the catalytic domain of neuropathy target esterase on the fluidity of bilayer lipid membranes","volume":"1798","author":"Greiner","year":"2010","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chang, P., He, L., Wang, Y., Heier, C., Wu, Y., and Huang, F. (2019). Characterization of the interaction of neuropathy target esterase with the endoplasmic reticulum and lipid droplets. Biomolecules, 9.","DOI":"10.3390\/biom9120848"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.taap.2006.08.002","article-title":"Phospholipase B activity and organophosphorus compound toxicity in cultured neural cells","volume":"219","author":"Read","year":"2007","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"37574","DOI":"10.1038\/srep37574","article-title":"Disturbed phospholipid homeostasis in endoplasmic reticulum initiates tri-o-cresyl phosphate-induced delayed neurotoxicity","volume":"6","author":"Zhu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.tox.2008.07.061","article-title":"The homeostasis of phosphatidylcholine and lysophosphatidylcholine was not disrupted during tri-o-cresyl phosphate-induced delayed neurotoxicity in hens","volume":"252","author":"Hou","year":"2008","journal-title":"Toxicology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/toxsci\/kfp068","article-title":"The homeostasis of phosphatidylcholine and lysophosphatidylcholine in nervous tissues of mice was not disrupted after administration of tri-o-cresyl phosphate","volume":"109","author":"Hou","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_50","first-page":"390","article-title":"Exposure to an organophosphate tocp drosophila melanogaster flies with altered activity of sws and its micrornas genes","volume":"35","author":"Tkachuk","year":"2019","journal-title":"Biopolym. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0306-4522(97)00388-6","article-title":"Neuropathy target esterase: Immunolocalization to neuronal cell bodies and axons","volume":"83","author":"Glynn","year":"1998","journal-title":"Neuroscience"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.cbi.2007.11.014","article-title":"Molecular cloning and expression analysis of cDNA ends of chicken neuropathy target esterase","volume":"172","author":"Chang","year":"2008","journal-title":"Chem. Biol. Interact."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.gene.2009.01.004","article-title":"Identification and characterization of chicken neuropathy target esterase","volume":"435","author":"Chang","year":"2009","journal-title":"Gene"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ryabova, E.V., Melentev, P.A., Komissarov, A.E., Surina, N.V., Ivanova, E.A., Matiytsiv, N., Shcherbata, H.R., and Sarantseva, S.V. (2021). Morpho-Functional Consequences of Swiss Cheese Knockdown in Glia of Drosophila melanogaster. Cells, 10.","DOI":"10.3390\/cells10030529"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1146\/annurev-ento-011118-112007","article-title":"Fat Body Biology in the Last Decade","volume":"64","author":"Li","year":"2019","journal-title":"Annu. Rev. Entomol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1534\/genetics.118.301583","article-title":"Triacylglycerol Metabolism in Drosophila melanogaster","volume":"210","author":"Heier","year":"2018","journal-title":"Genetics"},{"key":"ref_57","first-page":"13","article-title":"Comparative physiology of Malpighian tubules: Form and function","volume":"2016","author":"Nocelli","year":"2016","journal-title":"Insect Physiol"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Melentev, P.A., Sharapenkov, E.G., Surina, N.V., Ivanova, E.A., Ryabova, E.V., and Sarantseva, S.V. (2022). Drosophila Lysophospholipase Gene swiss cheese Is Required for Survival and Reproduction. Insects, 13.","DOI":"10.3390\/insects13010014"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1136\/jmedgenet-2014-102856","article-title":"Neuropathy target esterase impairments cause Oliver\u2013McFarlane and Laurence\u2013Moon syndromes","volume":"52","author":"Hufnagel","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/glia.23127","article-title":"NTE\/PNPLA6 is expressed in mature Schwann cells and is required for glial ensheathment of Remak fibers","volume":"65","author":"McFerrin","year":"2017","journal-title":"Glia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/15287390151126423","article-title":"Inhibition of calcium-stimulated ATPase in the hen brain P2 synaptosomal fraction by organophosphorus esters: Relevance to delayed neuropathy","volume":"63","author":"Barber","year":"2001","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_62","unstructured":"Huggins, D.J. (1982). Central Nervous System Endogenous Phosphorylation in Organophosphorus Delayed Neurotoxicity. [Ph.D. Thesis, University of Michigan]."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.cbi.2012.10.024","article-title":"Neuropathy target esterase (NTE): Overview and future","volume":"203","author":"Richardson","year":"2013","journal-title":"Chem. Biol. Interact."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1177\/0960327112446842","article-title":"Increased oxidative stress is associated with the development of organophosphate-induced delayed neuropathy","volume":"31","author":"Masoud","year":"2012","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/0041-008X(85)90162-0","article-title":"Phenylmethylsulfonyl fluoride protects rats from Mipafox-induced delayed neuropathy","volume":"81","author":"Veronesi","year":"1985","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1093\/toxsci\/62.2.274","article-title":"Effects of S-ethyl hexahydro-1H-azepine-1-carbothioate (molinate) on di-n-butyl dichlorovinyl phosphate (DBDCVP) neuropathy","volume":"62","author":"Moretto","year":"2001","journal-title":"Toxicol. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1515\/znc-1979-1-228","article-title":"Isolation of anatomical brain mutants of Drosophila by histological means","volume":"34","author":"Heisenberg","year":"1979","journal-title":"Z. F\u00fcr Nat. C"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"104520","DOI":"10.1016\/j.nbd.2019.104520","article-title":"ER responses play a key role in Swiss-Cheese\/Neuropathy Target Esterase-associated neurodegeneration","volume":"130","author":"Sunderhaus","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Melentev, P.A., Ryabova, E.V., Surina, N.V., Zhmujdina, D.R., Komissarov, A.E., Ivanova, E.A., Boltneva, N.P., Makhaeva, G.F., Sliusarenko, M.I., and Yatsenko, A.S. (2021). Loss of swiss cheese in neurons contributes to neurodegeneration with mitochondria abnormalities, reactive oxygen species acceleration and accumulation of lipid droplets in Drosophila brain. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158275"},{"key":"ref_70","first-page":"283","article-title":"Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function","volume":"9","author":"Dutta","year":"2016","journal-title":"Dis. Models Mech."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Sujkowski, A., Rainier, S., Fink, J.K., and Wessells, R.J. (2015). Delayed induction of human NTE (PNPLA6) rescues neurodegeneration and mobility defects of Drosophila swiss cheese (sws) mutants. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145356"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.3389\/fnins.2019.01207","article-title":"Disease-associated PNPLA6 mutations maintain partial functions when analyzed in Drosophila","volume":"13","author":"Sunderhaus","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_73","first-page":"404","article-title":"Knockdown of Pnpla6 protein results in motor neuron defects in zebrafish","volume":"6","author":"Song","year":"2013","journal-title":"Dis. Models Mech."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1128\/MCB.24.4.1667-1679.2004","article-title":"Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice","volume":"24","author":"Moser","year":"2004","journal-title":"Mol Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s11626-013-9691-4","article-title":"Functional pathways altered after silencing Pnpla6 (the codifying gene of neuropathy target esterase) in mouse embryonic stem cells under differentiation","volume":"50","author":"Pamies","year":"2014","journal-title":"Vitr. Cell. Dev. Biol. Anim."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00204-010-0518-8","article-title":"Expression of neuropathy target esterase in mouse embryonic stem cells during differentiation","volume":"84","author":"Pamies","year":"2010","journal-title":"Arch. Toxicol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.cbi.2016.07.030","article-title":"Roles of NTE protein and encoding gene in development and neurodevelopmental toxicity","volume":"259","author":"Sogorb","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.neuroscience.2014.08.031","article-title":"Silencing of PNPLA6, the neuropathy target esterase (NTE) codifying gene, alters neurodifferentiation of human embryonal carcinoma stem cells (NT2)","volume":"281","author":"Pamies","year":"2014","journal-title":"Neuroscience"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.cbi.2016.04.017","article-title":"Effects of mipafox, paraoxon, chlorpyrifos and its metabolite chlorpyrifos-oxon on the expression of biomarker genes of differentiation in D3 mouse embryonic stem cells","volume":"259","author":"Sogorb","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/ng1131","article-title":"Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity","volume":"33","author":"Winrow","year":"2003","journal-title":"Nat Genet"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5075","DOI":"10.1073\/pnas.0401030101","article-title":"Brain-specific deletion of neuropathy target esterase\/swisscheese results in neurodegeneration","volume":"101","author":"Akassoglou","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.toxlet.2012.03.004","article-title":"Involvement of neuropathy target esterase in tri-ortho-cresyl phosphate-induced testicular spermatogenesis failure and growth inhibition of spermatogonial stem cells in mice","volume":"211","author":"Chen","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.ajhg.2007.12.018","article-title":"Neuropathy target esterase gene mutations cause motor neuron disease","volume":"82","author":"Rainier","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/brain\/awt326","article-title":"PNPLA6 mutations cause Boucher-Neuh\u00e4user and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum","volume":"137","author":"Synofzik","year":"2014","journal-title":"Brain"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"100114","DOI":"10.1016\/j.prdoa.2021.100114","article-title":"Hereditary spastic paraplegia initially diagnosed as cerebral palsy","volume":"5","author":"Suchowersky","year":"2021","journal-title":"Clin. Parkinsonism Relat. Disord."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1007\/s00415-020-10028-w","article-title":"Bi-allelic variants in PNPLA6 possibly associated with Parkinsonian features in addition to spastic paraplegia phenotype","volume":"267","author":"Sen","year":"2020","journal-title":"J. Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"793547","DOI":"10.3389\/fneur.2021.793547","article-title":"Multifaceted and Age-Dependent Phenotypes Associated With Biallelic PNPLA6 Gene Variants: Eight Novel Cases and Review of the Literature","volume":"12","author":"Nanetti","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1007\/s00415-014-7555-9","article-title":"Boucher-Neuhauser syndrome: Cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: Two novel cases and a review of 40 cases from the literature","volume":"262","author":"Tarnutzer","year":"2015","journal-title":"J. Neurol."},{"key":"ref_89","first-page":"267","article-title":"Chorioretinal changes in a genetically confirmed case of Boucher-Neuh\u00e4user syndrome","volume":"40","author":"DeNaro","year":"2018","journal-title":"Retin. Cases Brief Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1080\/13816810.2021.1894461","article-title":"Chorioretinal dystrophy, hypogonadotropic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome due to a homozygous (c. 3524C> G (p. Ser1175Cys)) variant in PNPLA6 gene","volume":"42","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1080\/13816810.2019.1605392","article-title":"Detailed retinal phenotype of Boucher-Neuh\u00e4user syndrome associated with mutations in PNPLA6 mimicking choroideremia","volume":"40","author":"Serrano","year":"2019","journal-title":"Ophthalmic Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s12311-017-0909-y","article-title":"Different cerebellar ataxia phenotypes associated with mutations of the PNPLA6 gene in Brazilian patients with recessive ataxias","volume":"17","author":"Teive","year":"2018","journal-title":"Cerebellum"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/jhg.2015.3","article-title":"Novel mutations in the PNPLA6 gene in Boucher-Neuh\u00e4user syndrome","volume":"60","author":"Koh","year":"2015","journal-title":"J. Hum. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ejmg.2016.11.003","article-title":"Boucher Neuh\u00e4user Syndrome\u2013a rare cause of inherited hypogonadotropic hypogonadism. A case of two adult siblings with two novel mutations in PNPLA6","volume":"60","author":"Langdahl","year":"2017","journal-title":"Eur. J. Med. Genet."},{"key":"ref_95","first-page":"261","article-title":"A novel PNPLA6 compound heterozygous mutation identified in a Chinese patient with Boucher-Neuh\u00e4user syndrome","volume":"18","author":"Zheng","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1007\/s00415-014-7516-3","article-title":"Compound heterozygous PNPLA6 mutations cause Boucher-Neuh\u00e4user syndrome with late-onset ataxia","volume":"261","author":"Deik","year":"2014","journal-title":"J. Neurol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3988\/jcn.2022.18.2.233","article-title":"The First Korean Family with Boucher-Neuh\u00e4user Syndrome Carrying a Novel Mutation in PNPLA6","volume":"18","author":"Chung","year":"2022","journal-title":"J. Clin. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"810537","DOI":"10.3389\/fgene.2022.810537","article-title":"Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher-Neuh\u00e4user Syndrome","volume":"13","author":"He","year":"2022","journal-title":"Front. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"E2067","DOI":"10.1210\/jc.2014-1836","article-title":"Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome","volume":"99","author":"Topaloglu","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ensci.2018.11.022","article-title":"Gordon Holmes syndrome due to compound heterozygosity of two new PNPLA6 variants\u2013A diagnostic challenge","volume":"14","author":"Salgado","year":"2019","journal-title":"eNeurologicalSci"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Locci, S., Bianchi, S., Tessa, A., Santorelli, F.M., and Mignarri, A. (2021). Gordon Holmes syndrome caused by two novel mutations in the PNPLA6 gene. Clin. Neurol. Neurosurg., 106763.","DOI":"10.1016\/j.clineuro.2021.106763"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1007\/s10072-020-04869-6","article-title":"A novel PNPLA6 mutation in a Turkish family with intractable Holmes tremor and spastic ataxia","volume":"42","author":"Emekli","year":"2021","journal-title":"Neurol. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"145027","DOI":"10.1016\/j.gene.2020.145027","article-title":"Identification of Oliver-McFarlane syndrome caused by novel compound heterozygous variants of PNPLA6","volume":"761","author":"Liu","year":"2020","journal-title":"Gene"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jns.2018.06.016","article-title":"A new PNPLA6 mutation presenting as Oliver McFarlane syndrome","volume":"392","author":"Patsi","year":"2018","journal-title":"J. Neurol. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1080\/13816810.2021.1904419","article-title":"Oliver McFarlane syndrome: Two new cases and a review of the literature","volume":"42","author":"Lisbjerg","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1038\/s41598-018-20697-3","article-title":"The PKA-C3 catalytic subunit is required in two pairs of interneurons for successful mating of Drosophila","volume":"8","author":"Cassar","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1002\/jcb.25304","article-title":"PRKX, a Novel cAMP-Dependent Protein Kinase Member, Plays an Important Role in Development","volume":"117","author":"Huang","year":"2016","journal-title":"J. Cell. Biochem."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/4\/284\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:42:08Z","timestamp":1760136128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/4\/284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,24]]},"references-count":107,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["metabo12040284"],"URL":"https:\/\/doi.org\/10.3390\/metabo12040284","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,24]]}}}