{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:24:39Z","timestamp":1777580679206,"version":"3.51.4"},"reference-count":70,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TU492\/3-1"],"award-info":[{"award-number":["TU492\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TU2018"],"award-info":[{"award-number":["TU2018"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013220","name":"Ultragenyx","doi-asserted-by":"publisher","award":["TU492\/3-1"],"award-info":[{"award-number":["TU492\/3-1"]}],"id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013220","name":"Ultragenyx","doi-asserted-by":"publisher","award":["TU2018"],"award-info":[{"award-number":["TU2018"]}],"id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Long-chain 3-hydroxyacyl-CoA deficiency (LCHADD) and mitochondrial trifunctional protein (MTPD) belong to a group of inherited metabolic diseases affecting the degradation of long-chain chain fatty acids. During metabolic decompensation the incomplete degradation of fatty acids results in life-threatening episodes, coma and death. Despite fast identification at neonatal screening, LCHADD\/MTPD present with progressive neurodegenerative symptoms originally attributed to the accumulation of toxic hydroxyl acylcarnitines and energy deficiency. Recently, it has been shown that LCHADD human fibroblasts display a disease-specific alteration of complex lipids. Accumulating fatty acids, due to defective \u03b2-oxidation, contribute to a remodeling of several lipid classes including mitochondrial cardiolipins and sphingolipids. In the last years the face of LCHADD\/MTPD has changed. The reported dysregulation of complex lipids other than the simple acylcarnitines represents a novel aspect of disease development. Indeed, aberrant lipid profiles have already been associated with other neurodegenerative diseases such as Parkinson\u2019s Disease, Alzheimer\u2019s Disease, amyotrophic lateral sclerosis and retinopathy. Today, the physiopathology that underlies the development of the progressive neuropathic symptoms in LCHADD\/MTPD is not fully understood. Here, we hypothesize an alternative disease-causing mechanism that contemplates the interaction of several factors that acting in concert contribute to the heterogeneous clinical phenotype.<\/jats:p>","DOI":"10.3390\/ijms23137144","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T22:31:14Z","timestamp":1656369074000},"page":"7144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["An Altered Sphingolipid Profile as a Risk Factor for Progressive Neurodegeneration in Long-Chain 3-Hydroxyacyl-CoA Deficiency (LCHADD)"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3851-4843","authenticated-orcid":false,"given":"Sara","family":"Tucci","sequence":"first","affiliation":[{"name":"Pharmacy, Medical Center, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7039","DOI":"10.1073\/pnas.1801252115","article-title":"Cryo-EM structure of human mitochondrial trifunctional protein","volume":"115","author":"Liang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6069","DOI":"10.1073\/pnas.1816317116","article-title":"Crystal structure of human mitochondrial trifunctional protein, a fatty acid beta-oxidation metabolon","volume":"116","author":"Xia","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"473","DOI":"10.21037\/atm.2018.10.57","article-title":"Fatty acid oxidation disorders","volume":"6","author":"Merritt","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ymgme.2008.09.008","article-title":"A Delphi clinical practice protocol for the management of very long chain acyl-CoA dehydrogenase deficiency","volume":"96","author":"Arnold","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1007\/s10545-009-1126-8","article-title":"Treatment recommendations in long-chain fatty acid oxidation defects: Consensus from a workshop","volume":"32","author":"Spiekerkoetter","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/jimd.12377","article-title":"Regulatory news: Dojolvi (triheptanoin) as a source of calories and fatty acids in long-chain fatty acid oxidation disorders: FDA approval summary","volume":"44","author":"Zand","year":"2021","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Alatibi, K.I., Hagenbuchner, J., Wehbe, Z., Karall, D., Ausserlechner, M.J., Vockley, J., Spiekerkoetter, U., Grunert, S.C., and Tucci, S. (2021). Different Lipid Signature in Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders. Cells, 10.","DOI":"10.3390\/cells10051239"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alatibi, K.I., Tholen, S., Wehbe, Z., Hagenbuchner, J., Karall, D., Ausserlechner, M.J., Schilling, O., Grunert, S.C., Vockley, J., and Tucci, S. (2021). Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910556"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/j.ophtha.2016.06.048","article-title":"Characterization of Chorioretinopathy Associated with Mitochondrial Trifunctional Protein Disorders: Long-Term Follow-up of 21 Cases","volume":"123","author":"Boese","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJM199906033402204","article-title":"A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women","volume":"340","author":"Ibdah","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/ajg.2017.54","article-title":"Acute Fatty Liver Disease of Pregnancy: Updates in Pathogenesis, Diagnosis, and Management","volume":"112","author":"Liu","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_12","first-page":"595","article-title":"Mitochondrial fatty acid beta-oxidation in the retinal pigment epithelium","volume":"52","author":"Tyni","year":"2002","journal-title":"Pediatr. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.ymgme.2011.04.006","article-title":"Comprehensive cDNA study and quantitative analysis of mutant HADHA and HADHB transcripts in a French cohort of 52 patients with mitochondrial trifunctional protein deficiency","volume":"103","author":"Boutron","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.pediatrneurol.2008.12.017","article-title":"Mitochondrial trifunctional protein deficiency with recurrent rhabdomyolysis","volume":"40","author":"Scheuerman","year":"2009","journal-title":"Pediatr. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/humu.10211","article-title":"Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations","volume":"21","author":"Spiekerkoetter","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_16","first-page":"979","article-title":"Molecular characterization of mitochondrial trifunctional protein deficiency: Formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits","volume":"58","author":"Ushikubo","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Taylor, W.A., Mejia, E.M., Mitchell, R.W., Choy, P.C., Sparagna, G.C., and Hatch, G.M. (2012). Human trifunctional protein alpha links cardiolipin remodeling to beta-oxidation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048628"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/ncb3560","article-title":"Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin","volume":"19","author":"Ban","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.tcb.2017.08.011","article-title":"Phosphatidic Acid and Cardiolipin Coordinate Mitochondrial Dynamics","volume":"28","author":"Kameoka","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.biochi.2017.08.013","article-title":"Role of cardiolipin in stability of integral membrane proteins","volume":"142","author":"Musatov","year":"2017","journal-title":"Biochimie"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1128\/MCB.05603-11","article-title":"Mitochondrial fission contributes to mitochondrial dysfunction and insulin resistance in skeletal muscle","volume":"32","author":"Jheng","year":"2012","journal-title":"Mol. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"437","DOI":"10.3389\/fneur.2020.00437","article-title":"Exploring Sphingolipid Implications in Neurodegeneration","volume":"11","author":"Alessenko","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S1096-7192(02)00117-8","article-title":"Glucosylsphingosine accumulation in tissues from patients with Gaucher disease: Correlation with phenotype and genotype","volume":"76","author":"Orvisky","year":"2002","journal-title":"Mol. Genet. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1546-0096-5-15","article-title":"Farber disease: Clinical presentation, pathogenesis and a new approach to treatment","volume":"5","author":"Ehlert","year":"2007","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1126\/science.178.4065.1100","article-title":"Ceramidase deficiency in Farber\u2019s disease (lipogranulomatosis)","volume":"178","author":"Sugita","year":"1972","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"22","DOI":"10.2174\/1381612823666170828133059","article-title":"Alzheimer\u2019s Disease and Parkinson\u2019s Disease: A Review of Current Treatment Adopting a Nanotechnology Approach","volume":"24","author":"Trompetero","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"170069","DOI":"10.1098\/rsob.170069","article-title":"Sphingolipids: Membrane microdomains in brain development, function and neurological diseases","volume":"7","author":"Olsen","year":"2017","journal-title":"Open Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.semcdb.2020.10.008","article-title":"Sphingolipids metabolism alteration in the central nervous system: Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases","volume":"112","author":"Bouscary","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bandet, C.L., Tan-Chen, S., Bourron, O., Le Stunff, H., and Hajduch, E. (2019). Sphingolipid Metabolism: New Insight into Ceramide-Induced Lipotoxicity in Muscle Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030479"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.plipres.2014.01.004","article-title":"Ceramide: A simple sphingolipid with unique biophysical properties","volume":"54","author":"Castro","year":"2014","journal-title":"Prog. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Moskot, M., Bochenska, K., Jakobkiewicz-Banecka, J., Banecki, B., and Gabig-Ciminska, M. (2018). Abnormal Sphingolipid World in Inflammation Specific for Lysosomal Storage Diseases and Skin Disorders. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010247"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12944-019-0965-z","article-title":"Role of cholesterol and sphingolipids in brain development and neurological diseases","volume":"18","author":"Hussain","year":"2019","journal-title":"Lipids Health Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s10545-016-9915-3","article-title":"Unique plasma metabolomic signatures of individuals with inherited disorders of long-chain fatty acid oxidation","volume":"39","author":"McCoin","year":"2016","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.biocel.2016.12.015","article-title":"Fats for thoughts: An update on brain fatty acid metabolism","volume":"84","author":"Romano","year":"2017","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/jcbfm.1989.2","article-title":"ATP and brain function","volume":"9","author":"Erecinska","year":"1989","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/jcbfm.2013.128","article-title":"Why does brain metabolism not favor burning of fatty acids to provide energy? Reflections on disadvantages of the use of free fatty acids as fuel for brain","volume":"33","author":"Schonfeld","year":"2013","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_38","unstructured":"Siesjo, B.K. (1978). Brain energy metabolism and catecholaminergic activity in hypoxia, hypercapnia and ischemia. J. Neural Transm. Suppl., 17\u201322."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"246","DOI":"10.3389\/fncel.2019.00246","article-title":"Sphingolipids as Emerging Mediators in Retina Degeneration","volume":"13","author":"Vera","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1001\/archopht.1980.01020031079014","article-title":"Sandhoff\u2019s disease (GM2 gangliosidosis type 2). Histopathology and ultrastructure of the eye","volume":"98","author":"Brownstein","year":"1980","journal-title":"Arch. Ophthalmol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1001\/archopht.1978.03910050466015","article-title":"Optic nerve in globoid leukodystrophy (Krabbe\u2019s disease). Ultrastructural changes","volume":"96","author":"Brownstein","year":"1978","journal-title":"Arch. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.survophthal.2013.02.005","article-title":"Beyond the cherry-red spot: Ocular manifestations of sphingolipid-mediated neurodegenerative and inflammatory disorders","volume":"59","author":"Chen","year":"2014","journal-title":"Surv. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1136\/bjo.57.12.885","article-title":"Ultrastructure of the optic nerve in Krabbe\u2019s leucodystrophy","volume":"57","author":"Harcourt","year":"1973","journal-title":"Br. J. Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s10495-015-1109-1","article-title":"Tumor suppressive functions of ceramide: Evidence and mechanisms","volume":"20","author":"Galadari","year":"2015","journal-title":"Apoptosis"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"20063","DOI":"10.1073\/pnas.0911028106","article-title":"Ceramide kinase regulates phospholipase C and phosphatidylinositol 4, 5, bisphosphate in phototransduction","volume":"106","author":"Dasgupta","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.1167\/iovs.16-19717","article-title":"Suppression of Acid Sphingomyelinase Protects the Retina from Ischemic Injury","volume":"57","author":"Fan","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00417-008-0957-6","article-title":"Ceramide production associated with retinal apoptosis after retinal detachment","volume":"247","author":"Ranty","year":"2009","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1194\/jlr.M082198","article-title":"Overexpression of acid ceramidase (ASAH1) protects retinal cells (ARPE19) from oxidative stress","volume":"60","author":"Sugano","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1620\/tjem.190.223","article-title":"Ceramide-induced cell death in cultured rat retinal pigment epithelial cells","volume":"190","author":"Tomita","year":"2000","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12944-021-01466-0","article-title":"Sphingolipid lysosomal storage diseases: From bench to bedside","volume":"20","author":"Khodour","year":"2021","journal-title":"Lipids Health Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s11101-018-9588-7","article-title":"Polar lipids in cosmetics: Recent trends in extraction, separation, analysis and main applications","volume":"17","author":"Traversier","year":"2018","journal-title":"Phytochem. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1046\/j.1471-4159.2001.00310.x","article-title":"Cerebroside synthesis as a measure of the rate of remyelination following cuprizone-induced demyelination in brain","volume":"77","author":"Jurevics","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/BF00685311","article-title":"Fatty acid composition of cerebrosides and cerebroside sulphatides in cerebral oedema","volume":"12","author":"Yanagihara","year":"1968","journal-title":"Acta Neuropathol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pujol-Lereis, L.M. (2019). Alteration of Sphingolipids in Biofluids: Implications for Neurodegenerative Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143564"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mielke, M.M., Maetzler, W., Haughey, N.J., Bandaru, V.V., Savica, R., Deuschle, C., Gasser, T., Hauser, A.K., Graber-Sultan, S., and Schleicher, E. (2013). Plasma ceramide and glucosylceramide metabolism is altered in sporadic Parkinson\u2019s disease and associated with cognitive impairment: A pilot study. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073094"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Pujol-Lereis, L.M., Liebisch, G., Schick, T., Lin, Y., Grassmann, F., Uchida, K., Zipfel, P.F., Fauser, S., Skerka, C., and Weber, B.H.F. (2018). Evaluation of serum sphingolipids and the influence of genetic risk factors in age-related macular degeneration. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200739"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1093\/brain\/awu139","article-title":"Cerebrospinal fluid ceramides from patients with multiple sclerosis impair neuronal bioenergetics","volume":"137","author":"Vidaurre","year":"2014","journal-title":"Brain"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bbadis.2009.08.012","article-title":"Mitochondrial dysfunction in amyotrophic lateral sclerosis","volume":"1802","author":"Shi","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"246","DOI":"10.2174\/156652411795243450","article-title":"The Role of immune and inflammatory mechanisms in ALS","volume":"11","author":"McCombe","year":"2011","journal-title":"Curr. Mol. Med."},{"key":"ref_60","first-page":"5968","article-title":"Hydroxylated Long-Chain Acylcarnitines are Biomarkers of Mitochondrial Myopathy","volume":"104","author":"Vissing","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.neuint.2010.03.025","article-title":"Long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies induce oxidative stress in rat brain","volume":"56","author":"Tonin","year":"2010","journal-title":"Neurochem. Int."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Natarajan, S.K., and Ibdah, J.A. (2018). Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010322"},{"key":"ref_63","first-page":"2003","article-title":"Oxidative stress, mitochondrial damage and neurodegenerative diseases","volume":"8","author":"Guo","year":"2013","journal-title":"Neural Regen. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/01616412.2016.1251711","article-title":"Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders","volume":"39","author":"Islam","year":"2017","journal-title":"Neurol Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.freeradbiomed.2004.04.007","article-title":"Inflammatory mediator and beta-amyloid (25-35)-induced ceramide generation and iNOS expression are inhibited by vitamin E","volume":"37","author":"Ayasolla","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.exger.2005.07.003","article-title":"Enhanced anti-oxidant protection of liver membranes in long-lived rats fed on a coenzyme Q10-supplemented diet","volume":"40","author":"Bello","year":"2005","journal-title":"Exp. Gerontol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/s42255-019-0134-8","article-title":"Metabolic Messengers: Ceramides","volume":"1","author":"Summers","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2326409817701472","DOI":"10.1177\/2326409817701472","article-title":"Mechanistic Bases of Neurotoxicity Provoked by Fatty Acids Accumulating in MCAD and LCHAD Deficiencies","volume":"5","author":"Amaral","year":"2017","journal-title":"J. Inborn Errors Metab. Screen."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1038\/s41598-018-21519-2","article-title":"Very long-\/and long Chain-3-Hydroxy Acyl CoA Dehydrogenase Deficiency correlates with deregulation of the mitochondrial fusion\/fission machinery","volume":"8","author":"Hagenbuchner","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10545-013-9663-6","article-title":"Dietary triheptanoin rescues oligodendrocyte loss, dysmyelination and motor function in the nur7 mouse model of Canavan disease","volume":"37","author":"Francis","year":"2014","journal-title":"J. Inherit. Metab. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7144\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:20Z","timestamp":1760139560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,27]]},"references-count":70,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23137144"],"URL":"https:\/\/doi.org\/10.3390\/ijms23137144","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,27]]}}}