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Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease
  1. 1.

    Ray Dorsey, E. et al. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 17, 939–953 (2018).

    Article  Google Scholar 

  2. 2.

    Dauer, W. & Przedborski, S. Parkinson’s disease: mechanisms and models. Neuron 39, 889–909 (2003).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  3. 3.

    Kalia, L. V. & Lang, A. E. Parkinson’s disease. Lancet 386, 896–912 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Obeso, J. A. Past, present, and future of Parkinson’s disease. Mov. Disord. 32, 1263–1263 (2017).

    Article  Google Scholar 

  5. 5.

    Marsili, L., Rizzo, G. & Colosimo, C. Diagnostic criteria for Parkinson’s disease: from James Parkinson to the concept of prodromal disease. Front. Neurol. 9, 1–10 (2018).

    Article  Google Scholar 

  6. 6.

    Goetz, C. G. et al. Movement disorder society-sponsored revision of the unified Parkinson’s disease rating scale (MDS-UPDRS): process, format, and clinimetric testing plan. Mov. Disord. 22, 41–47 (2007).

    MathSciNet  PubMed  Article  Google Scholar 

  7. 7.

    Gelb, D. J., Oliver, E. & Gilman, S. Diagnostic criteria for Parkinson disease. Arch. Neurol. 56, 33–39 (1999).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  8. 8.

    Jankovic, J. Parkinson’s disease clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry 79, 386–376 (2008).

    Article  Google Scholar 

  9. 9.

    Hawkes, C. H. The prodromal phase of sporadic Parkinson’s disease: Does it exist and if so how long is it? Mov. Disord. 23, 1799–1807 (2008).

    PubMed  Article  Google Scholar 

  10. 10.

    Hawkes, C. H., Del Tredici, K. & Braak, H. A timeline for Parkinson’s disease. Park. Relat. Disord. 16, 79–84 (2010).

    Article  Google Scholar 

  11. 11.

    Ravn, A.-H., Thyssen, J. P. & Egeberg, A. Skin disorders in Parkinson’s disease: potential biomarkers and risk factors. Clin. Cosmet. Investig. Dermatol. 10, 87–92 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Mastrolonardo, M., Diaferio, A. & Logroscino, G. Seborrheic dermatitis, increased sebum excretion, and Parkinson’s disease: a survey of (im) possible links. Med. Hypotheses 60, 907–911 (2003).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    Stewart, M. E. & Downing, D. T. Chemistry and Function of Mammalian Sebaceous Lipids. Advances in Lipid Research vol. 24 (Academic Press, 1991).

  14. 14.

    Lovászi, M., Szegedi, A., Zouboulis, C. C. & Törőcsik, D. Sebaceous-immunobiology is orchestrated by sebum lipids. Dermatoendocrinology 9, 1–10 (2018).

    Google Scholar 

  15. 15.

    Picardo, M. et al. Sebaceous gland lipids. Dermatoendocrinology 1, 68–71 (2009).

    CAS  Article  Google Scholar 

  16. 16.

    Trivedi, D. K. et al. Discovery of volatile biomarkers of Parkinson’s disease from sebum. ACS Cent. Sci. 5, 599–606 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Dunn, W. B., Broadhurst, D. I., Atherton, H. J., Goodacre, R. & Griffin, J. L. Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chem. Soc. Rev. 40, 387–426 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  18. 18.

    Dunn, W. B. et al. Mass appeal: metabolite identification in mass spectrometry-focused untargeted metabolomics. Metabolomics 9, 44–66 (2013).

    CAS  Article  Google Scholar 

  19. 19.

    Shao, Y. & Le, W. Recent advances and perspectives of metabolomics-based investigations in Parkinson’s disease. Mol. Neurodegener. 14, 1–12 (2019).

    CAS  Article  Google Scholar 

  20. 20.

    Cova, I. & Priori, A. Diagnostic biomarkers for Parkinson’s disease at a glance: where are we? J. Neural Transm. 125, 1417–1432 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  21. 21.

    Havelund, J. F., Heegaard, N. H. H., Færgeman, N. J. K. & Gramsbergen, J. B. Biomarker research in Parkinson’s disease using metabolite profiling. Metabolites 7, 42 (2017).

  22. 22.

    Goldstein, D. S., Holmes, C., Lopez, G. J., Wu, T. & Sharabi, Y. Cerebrospinal fluid biomarkers of central dopamine deficiency predict Parkinson’s disease. Park. Relat. Disord. 50, 108–112 (2018).

    Article  Google Scholar 

  23. 23.

    Mattsson, N. CSF biomarkers in neurodegenerative diseases. Clin. Chem. Lab. Med. 49, 345–352 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  24. 24.

    Engelborghs, S., Marescau, B. & De Deyn, P. P. Amino acids and biogenic amines in cerebrospinal fluid of patients with Parkinson’s disease. Neurochem. Res. 28, 1145–1150 (2003).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  25. 25.

    Hong, Z. et al. DJ-1 and α-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 133, 713–726 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    D’Andrea, G. et al. Different circulating trace amine profiles in de novo and treated Parkinson’s disease patients. Sci. Rep. 9, 1–11 (2019).

    Article  CAS  Google Scholar 

  27. 27.

    LeWitt, P. A. et al. Metabolomic biomarkers as strong correlates of Parkinson disease progression. Neurology 88, 862–869 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Saiki, S. et al. Decreased long-chain acylcarnitines from insufficient β-oxidation as potential early diagnostic markers for Parkinson’s disease. Sci. Rep. 7, 1–15 (2017).

    ADS  Article  CAS  Google Scholar 

  29. 29.

    Cipriani, S., Chen, X. & Schwarzschild, M. A. Urate: a novel biomarker of Parkinsons disease risk, diagnosis and prognosis. Biomark. Med. 4, 701–712 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Moisan, F. et al. Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis. J. Neurol. Neurosurg. Psychiatry 87, 952–957 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Chawla, N. V., Bowyer, K. W., Hall, L. O. & Kegelmeyer, P. W. SMOTE: synthetic minority over-sampling technique. J. Artif. Intell. Res. 16, 321–357 (2002).

    MATH  Article  Google Scholar 

  32. 32.

    Sumner, L. W. et al. Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Inititative (MSI). Metabolomics 3, 211–221 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Liebisch, G. et al. Shorthand notation for lipid structures derived from mass spectrometry. J. Lipid Res. 54, 1523–1530 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Li, S. et al. Predicting network activity from high throughput metabolomics. PLoS Comput. Biol. 9, e1003123 (2013).

  35. 35.

    Longo, N., Frigeni, M., Pasquali, M., Biophys, B. & Author, A. Carnitine transport and fatty acid oxidation. Biochim. Biophys. Acta 1863, 2422–2435 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Rattray, N. J. W. et al. Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty. Nat. Commun. 10, 1–12 (2019).

    CAS  Article  Google Scholar 

  37. 37.

    Alecu, I. & Bennett, S. A. L. Dysregulated lipid metabolism and its role in α-synucleinopathy in Parkinson’s disease. Front. Neurosci. 13, 1–22 (2019).

    Article  Google Scholar 

  38. 38.

    Lin, G., Wang, L., Marcogliese, P. C. & Bellen, H. J. Sphingolipids in the pathogenesis of Parkinson’s disease and Parkinsonism. Trends Endocrinol. Metab. 30, 106–117 (2019).

    CAS  Article  Google Scholar 

  39. 39.

    Donadio, V. et al. Skin nerve alpha-synuclein deposits: a biomarker for idiopathic Parkinson disease. Neurology 82, 1362–1369 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Xicoy, H., Wieringa, B. & Martens, G. J. M. The role of lipids in Parkinson’s disease. Cells 8, 27 (2019).

    CAS  PubMed Central  Article  Google Scholar 

  41. 41.

    Indellicato, R. & Trinchera, M. The link between Gaucher disease and Parkinson’s disease sheds light on old and novel disorders of sphingolipid metabolism. Int. J. Mol. Sci. 20, 3304 (2019).

    CAS  PubMed Central  Article  Google Scholar 

  42. 42.

    Isacson, O., Brekk, O. R. & Hallett, P. J. Novel results and concepts emerging from lipid cell biology relevant to degenerative brain aging and disease. Front. Neurol. 10, 1–8 (2019).

    Article  Google Scholar 

  43. 43.

    Hallett, P. J., Engelender, S. & Isacson, O. Lipid and immune abnormalities causing age-dependent neurodegeneration and Parkinson’s disease. J. Neuroinflamm. 16, 1–15 (2019).

    CAS  Article  Google Scholar 

  44. 44.

    Hoyo, P. et al. Oxidative stress in skin fibroblasts cultures from patients with Parkinson’ s disease. BMC Neurol. 10, 1–7 (2010).

    Article  Google Scholar 

  45. 45.

    Mortiboys, H. et al. Mitochondrial function and morphology are impaired in parkin mutant fibroblasts. Ann. Neurol. 64, 555–565 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Kurz, J., Parnham, M. J., Geisslinger, G. & Schiffmann, S. Ceramides as novel disease biomarkers. Trends Mol. Med. 25, 20–32 (2019).

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Plotegher, N., Bubacco, L., Greggio, E. & Civiero, L. Ceramides in Parkinson’s disease: from recent evidence to new hypotheses. Front. Neurosci. 13, 1–7 (2019).

    Article  Google Scholar 

  48. 48.

    Mielke, M. M. et al. Plasma ceramide and glucosylceramide metabolism is altered in sporadic Parkinson’s disease and associated with cognitive impairment: a pilot study. PLoS ONE 8, 1–6 (2013).

    Article  CAS  Google Scholar 

  49. 49.

    Gulati, S., Liu, Y., Munkacsi, A. B., Wilcox, L. & Sturley, S. L. Sterols and sphingolipids: dynamic duo or partners in crime? Prog. Lipid Res. 49, 353–365 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 50.

    Liang, J. J. & Rasmusson, A. M. Overview of the molecular steps in steroidogenesis of the GABAergic neurosteroids allopregnanolone and pregnanolone. Chronic Stress 2, 247054701881855 (2018).

    Article  Google Scholar 

  51. 51.

    Verschuur, C. V. M. et al. Randomized delayed-start trial of levodopa in Parkinson’s disease. N. Engl. J. Med. 380, 315–324 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  52. 52.

    Dunn, W. B. et al. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat. Protoc. 6, 1060–1083 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

Original Text (This is the original text for your reference.)

  1. 1.

    Ray Dorsey, E. et al. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 17, 939–953 (2018).

    Article  Google Scholar 

  2. 2.

    Dauer, W. & Przedborski, S. Parkinson’s disease: mechanisms and models. Neuron 39, 889–909 (2003).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  3. 3.

    Kalia, L. V. & Lang, A. E. Parkinson’s disease. Lancet 386, 896–912 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Obeso, J. A. Past, present, and future of Parkinson’s disease. Mov. Disord. 32, 1263–1263 (2017).

    Article  Google Scholar 

  5. 5.

    Marsili, L., Rizzo, G. & Colosimo, C. Diagnostic criteria for Parkinson’s disease: from James Parkinson to the concept of prodromal disease. Front. Neurol. 9, 1–10 (2018).

    Article  Google Scholar 

  6. 6.

    Goetz, C. G. et al. Movement disorder society-sponsored revision of the unified Parkinson’s disease rating scale (MDS-UPDRS): process, format, and clinimetric testing plan. Mov. Disord. 22, 41–47 (2007).

    MathSciNet  PubMed  Article  Google Scholar 

  7. 7.

    Gelb, D. J., Oliver, E. & Gilman, S. Diagnostic criteria for Parkinson disease. Arch. Neurol. 56, 33–39 (1999).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  8. 8.

    Jankovic, J. Parkinson’s disease clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry 79, 386–376 (2008).

    Article  Google Scholar 

  9. 9.

    Hawkes, C. H. The prodromal phase of sporadic Parkinson’s disease: Does it exist and if so how long is it? Mov. Disord. 23, 1799–1807 (2008).

    PubMed  Article  Google Scholar 

  10. 10.

    Hawkes, C. H., Del Tredici, K. & Braak, H. A timeline for Parkinson’s disease. Park. Relat. Disord. 16, 79–84 (2010).

    Article  Google Scholar 

  11. 11.

    Ravn, A.-H., Thyssen, J. P. & Egeberg, A. Skin disorders in Parkinson’s disease: potential biomarkers and risk factors. Clin. Cosmet. Investig. Dermatol. 10, 87–92 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Mastrolonardo, M., Diaferio, A. & Logroscino, G. Seborrheic dermatitis, increased sebum excretion, and Parkinson’s disease: a survey of (im) possible links. Med. Hypotheses 60, 907–911 (2003).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    Stewart, M. E. & Downing, D. T. Chemistry and Function of Mammalian Sebaceous Lipids. Advances in Lipid Research vol. 24 (Academic Press, 1991).

  14. 14.

    Lovászi, M., Szegedi, A., Zouboulis, C. C. & Törőcsik, D. Sebaceous-immunobiology is orchestrated by sebum lipids. Dermatoendocrinology 9, 1–10 (2018).

    Google Scholar 

  15. 15.

    Picardo, M. et al. Sebaceous gland lipids. Dermatoendocrinology 1, 68–71 (2009).

    CAS  Article  Google Scholar 

  16. 16.

    Trivedi, D. K. et al. Discovery of volatile biomarkers of Parkinson’s disease from sebum. ACS Cent. Sci. 5, 599–606 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Dunn, W. B., Broadhurst, D. I., Atherton, H. J., Goodacre, R. & Griffin, J. L. Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chem. Soc. Rev. 40, 387–426 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  18. 18.

    Dunn, W. B. et al. Mass appeal: metabolite identification in mass spectrometry-focused untargeted metabolomics. Metabolomics 9, 44–66 (2013).

    CAS  Article  Google Scholar 

  19. 19.

    Shao, Y. & Le, W. Recent advances and perspectives of metabolomics-based investigations in Parkinson’s disease. Mol. Neurodegener. 14, 1–12 (2019).

    CAS  Article  Google Scholar 

  20. 20.

    Cova, I. & Priori, A. Diagnostic biomarkers for Parkinson’s disease at a glance: where are we? J. Neural Transm. 125, 1417–1432 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  21. 21.

    Havelund, J. F., Heegaard, N. H. H., Færgeman, N. J. K. & Gramsbergen, J. B. Biomarker research in Parkinson’s disease using metabolite profiling. Metabolites 7, 42 (2017).

  22. 22.

    Goldstein, D. S., Holmes, C., Lopez, G. J., Wu, T. & Sharabi, Y. Cerebrospinal fluid biomarkers of central dopamine deficiency predict Parkinson’s disease. Park. Relat. Disord. 50, 108–112 (2018).

    Article  Google Scholar 

  23. 23.

    Mattsson, N. CSF biomarkers in neurodegenerative diseases. Clin. Chem. Lab. Med. 49, 345–352 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  24. 24.

    Engelborghs, S., Marescau, B. & De Deyn, P. P. Amino acids and biogenic amines in cerebrospinal fluid of patients with Parkinson’s disease. Neurochem. Res. 28, 1145–1150 (2003).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  25. 25.

    Hong, Z. et al. DJ-1 and α-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain 133, 713–726 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    D’Andrea, G. et al. Different circulating trace amine profiles in de novo and treated Parkinson’s disease patients. Sci. Rep. 9, 1–11 (2019).

    Article  CAS  Google Scholar 

  27. 27.

    LeWitt, P. A. et al. Metabolomic biomarkers as strong correlates of Parkinson disease progression. Neurology 88, 862–869 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Saiki, S. et al. Decreased long-chain acylcarnitines from insufficient β-oxidation as potential early diagnostic markers for Parkinson’s disease. Sci. Rep. 7, 1–15 (2017).

    ADS  Article  CAS  Google Scholar 

  29. 29.

    Cipriani, S., Chen, X. & Schwarzschild, M. A. Urate: a novel biomarker of Parkinsons disease risk, diagnosis and prognosis. Biomark. Med. 4, 701–712 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Moisan, F. et al. Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis. J. Neurol. Neurosurg. Psychiatry 87, 952–957 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Chawla, N. V., Bowyer, K. W., Hall, L. O. & Kegelmeyer, P. W. SMOTE: synthetic minority over-sampling technique. J. Artif. Intell. Res. 16, 321–357 (2002).

    MATH  Article  Google Scholar 

  32. 32.

    Sumner, L. W. et al. Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Inititative (MSI). Metabolomics 3, 211–221 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Liebisch, G. et al. Shorthand notation for lipid structures derived from mass spectrometry. J. Lipid Res. 54, 1523–1530 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Li, S. et al. Predicting network activity from high throughput metabolomics. PLoS Comput. Biol. 9, e1003123 (2013).

  35. 35.

    Longo, N., Frigeni, M., Pasquali, M., Biophys, B. & Author, A. Carnitine transport and fatty acid oxidation. Biochim. Biophys. Acta 1863, 2422–2435 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Rattray, N. J. W. et al. Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty. Nat. Commun. 10, 1–12 (2019).

    CAS  Article  Google Scholar 

  37. 37.

    Alecu, I. & Bennett, S. A. L. Dysregulated lipid metabolism and its role in α-synucleinopathy in Parkinson’s disease. Front. Neurosci. 13, 1–22 (2019).

    Article  Google Scholar 

  38. 38.

    Lin, G., Wang, L., Marcogliese, P. C. & Bellen, H. J. Sphingolipids in the pathogenesis of Parkinson’s disease and Parkinsonism. Trends Endocrinol. Metab. 30, 106–117 (2019).

    CAS  Article  Google Scholar 

  39. 39.

    Donadio, V. et al. Skin nerve alpha-synuclein deposits: a biomarker for idiopathic Parkinson disease. Neurology 82, 1362–1369 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Xicoy, H., Wieringa, B. & Martens, G. J. M. The role of lipids in Parkinson’s disease. Cells 8, 27 (2019).

    CAS  PubMed Central  Article  Google Scholar 

  41. 41.

    Indellicato, R. & Trinchera, M. The link between Gaucher disease and Parkinson’s disease sheds light on old and novel disorders of sphingolipid metabolism. Int. J. Mol. Sci. 20, 3304 (2019).

    CAS  PubMed Central  Article  Google Scholar 

  42. 42.

    Isacson, O., Brekk, O. R. & Hallett, P. J. Novel results and concepts emerging from lipid cell biology relevant to degenerative brain aging and disease. Front. Neurol. 10, 1–8 (2019).

    Article  Google Scholar 

  43. 43.

    Hallett, P. J., Engelender, S. & Isacson, O. Lipid and immune abnormalities causing age-dependent neurodegeneration and Parkinson’s disease. J. Neuroinflamm. 16, 1–15 (2019).

    CAS  Article  Google Scholar 

  44. 44.

    Hoyo, P. et al. Oxidative stress in skin fibroblasts cultures from patients with Parkinson’ s disease. BMC Neurol. 10, 1–7 (2010).

    Article  Google Scholar 

  45. 45.

    Mortiboys, H. et al. Mitochondrial function and morphology are impaired in parkin mutant fibroblasts. Ann. Neurol. 64, 555–565 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Kurz, J., Parnham, M. J., Geisslinger, G. & Schiffmann, S. Ceramides as novel disease biomarkers. Trends Mol. Med. 25, 20–32 (2019).

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Plotegher, N., Bubacco, L., Greggio, E. & Civiero, L. Ceramides in Parkinson’s disease: from recent evidence to new hypotheses. Front. Neurosci. 13, 1–7 (2019).

    Article  Google Scholar 

  48. 48.

    Mielke, M. M. et al. Plasma ceramide and glucosylceramide metabolism is altered in sporadic Parkinson’s disease and associated with cognitive impairment: a pilot study. PLoS ONE 8, 1–6 (2013).

    Article  CAS  Google Scholar 

  49. 49.

    Gulati, S., Liu, Y., Munkacsi, A. B., Wilcox, L. & Sturley, S. L. Sterols and sphingolipids: dynamic duo or partners in crime? Prog. Lipid Res. 49, 353–365 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 50.

    Liang, J. J. & Rasmusson, A. M. Overview of the molecular steps in steroidogenesis of the GABAergic neurosteroids allopregnanolone and pregnanolone. Chronic Stress 2, 247054701881855 (2018).

    Article  Google Scholar 

  51. 51.

    Verschuur, C. V. M. et al. Randomized delayed-start trial of levodopa in Parkinson’s disease. N. Engl. J. Med. 380, 315–324 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  52. 52.

    Dunn, W. B. et al. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat. Protoc. 6, 1060–1083 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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