SLAS Discovery - Special Issue on Advances in MALDI Mass Spectrometry for Drug Discovery - Volume 22 Issue 10 - December 2017 - 1227

Jones et al.
size. This type of workflow could be fortuitous in studies
monitoring GSL species accumulation following the administration of GluCer synthase inhibitors or other molecules
designed to knock down GSL synthesis. This could be particularly useful for neuropathic GD and other GSL storage
diseases, such as metachromatic leukodystrophy affected
by sulfatide storage, Sandhoff disease affected by GM2
accumulation,30,42 and Krabbe disease affected by GalCer
accumulation.43
Acknowledgments
The authors thank Venette Inskeep and Brian Quinn for technical
assistance.

Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
This work was supported by grants from the National Institutes of
Health (R01 DK36729 to G.A.G. and R01 NS086134 in part to
Y.S.) and a Cincinnati Children's Hospital Medical Center RIP
Award to Y.S. Partial support of these studies was from the South
Carolina Centers of Economic Excellence SmartState Endowed
Chair Program to R.R.D.

References
1. Sandhoff, K.; Kolter, T.; Van Echten-Deckert, G. Sphingolipid
Metabolism. Sphingoid Analogs, Sphingolipid Activator
Proteins, and the Pathology of the Cell. Ann. N.Y. Acad. Sci.
1998, 845, 139-151.
2. Grabowski, G. A.; Petsko, G. A.; Kolodny, E. H. Gaucher
Disease. In The Online Metabolic and Molecular Bases of
Inherited Diseases; Valle, D.; Beaudet, A.; Vogelstein, B.;
et al., Eds.; McGraw-Hill Companies: New York, 2010;
Chapter 146.
3. Burrow, T. A.; Sun, Y.; Prada, C. E.; et al. CNS, Lung, and
Lymph Node Involvement in Gaucher Disease Type 3 after 11
Years of Therapy: Clinical, Histopathologic, and Biochemical
Findings. Mol. Genet. Metab. 2015, 114 (2), 233-241.
4. Elstein, D.; Alcalay, R.; Zimran, A. The Emergence of
Parkinson Disease among Patients with Gaucher Disease.
Best Pract. Res. Clin. Endocrinol. Metab. 2015, 29 (2), 249-
259.
5. Sidransky, E.; Nalls, M. A.; Aasly, J. O.; et al. Multicenter
Analysis of Glucocerebrosidase Mutations in Parkinson's
Disease. N. Engl. J. Med. 2009, 361 (17), 1651-1661.
6. Nichols, W. C.; Pankratz, N.; Marek, D. K.; et al. Mutations
in GBA Are Associated with Familial Parkinson Disease
Susceptibility and Age at Onset. Neurology 2009, 72 (4),
310-316.
7. Zimran, A.; Pastores, G. M.; Tylki-Szymanska, A.; et al.
Safety and Efficacy of Velaglucerase Alfa in Gaucher Disease
Type 1 Patients Previously Treated with Imiglucerase. Am. J.
Hematol. 2013, 88 (3), 172-178.

1227
8. Starzyk, K.; Richards, S.; Yee, J.; et al. The Long-Term
International Safety Experience of Imiglucerase Therapy for
Gaucher Disease. Mol. Genet. Metab. 2007, 90 (2), 157-163.
9. Marshall, J.; Sun, Y.; Bangari, D. S.; et al. CNS-Accessible
Inhibitor of Glucosylceramide Synthase for Substrate
Reduction Therapy of Neuronopathic Gaucher Disease. Mol.
Ther. 2016, 24 (6), 1019-1029.
10. Radin, N. S. Treatment of Gaucher Disease with an Enzyme
Inhibitor. Glycoconj. J. 1996, 13 (2), 153-157.
11. Sardi, S. P.; Viel, C.; Clarke, J.; et al. Glucosylceramide
Synthase Inhibition Alleviates Aberrations in Synucleinopathy
Models. Proc. Natl. Acad. Sci U.S.A. 2017, 114 (10), 2699-
2704.
12. Sun, Y.; Zhang, W.; Xu, Y. H.; et al. Substrate Compositional
Variation with Tissue/Region and Gba1 Mutations in Mouse
Models-Implications for Gaucher Disease. PLoS One 2013,
8 (3), e57560.
13. Boutin, M.; Sun, Y.; Shacka, J. J.; et al. Tandem Mass
Spectrometry Multiplex Analysis of Glucosylceramide and
Galactosylceramide Isoforms in Brain Tissues at Different Stages
of Parkinson Disease. Anal. Chem. 2016, 88 (3), 1856-1863.
14. Schapira, A. H.; Chiasserini, D.; Beccari, T.; et al.
Glucocerebrosidase in Parkinson's Disease: Insights into
Pathogenesis and Prospects for Treatment. Mov. Disord. 2016,
31 (6), 830-835.
15. Mazzulli, J. R.; Xu, Y. H.; Sun, Y.; et al. Gaucher
Disease Glucocerebrosidase and Alpha-Synuclein Form a
Bidirectional Pathogenic Loop in Synucleinopathies. Cell
2011, 146 (1), 37-52.
16. Couto, D.; Santinha, D.; Melo, T.; et al. Glycosphingolipids
and Oxidative Stress: Evaluation of Hydroxyl Radical
Oxidation of Galactosyl and Lactosylceramides Using Mass
Spectrometry. Chem. Phys. Lipids 2015, 191, 106-114.
17. Gessel, M. M.; Norris, J. L.; Caprioli, R. M. MALDI Imaging
Mass Spectrometry: Spatial Molecular Analysis to Enable a
New Age of Discovery. J. Proteomics 2014, 107, 71-82.
18. Aichler, M.; Walch, A. MALDI Imaging Mass Spectrometry:
Current Frontiers and Perspectives in Pathology Research and
Practice. Lab. Invest. 2015, 95 (4), 422-431.
19. Spraggins, J. M.; Rizzo, D. G.; Moore, J. L.; et al. MALDI
FTICR IMS of Intact Proteins: Using Mass Accuracy to
Link Protein Images with Proteomics Data. J. Am. Soc. Mass
Spectrom. 2015, 26 (6), 974-985.
20. Yalcin, E. B.; de la Monte, S. M. Review of Matrix-Assisted
Laser Desorption Ionization-Imaging Mass Spectrometry for
Lipid Biochemical Histopathology. J. Histochem. Cytochem.
2015, 63 (10), 762-771.
21. Jones, E. E.; Dworski, S.; Canals, D.; et al. On-Tissue
Localization of Ceramides and Other Sphingolipids by
MALDI Mass Spectrometry Imaging. Anal. Chem. 2014, 86
(16), 8303-8311.
22. Vens-Cappell, S.; Kouzel, I. U.; Kettling, H.; et al. On-Tissue
Phospholipase C Digestion for Enhanced MALDI-MS
Imaging of Neutral Glycosphingolipids. Anal. Chem. 2016,
88 (11), 5595-5599.
23. Wang, H. Y.; Jackson, S. N.; Post, J.; et al. A Minimalist
Approach to MALDI Imaging of Glycerophospholipids and
Sphingolipids in Rat Brain Sections. Int. J. Mass Spectrom.
2008, 278 (2-3), 143-149.
Table of Contents for the Digital Edition of SLAS Discovery - Special Issue on Advances in MALDI Mass Spectrometry for Drug Discovery - Volume 22 Issue 10 - December 2017
