Heat shock protein-based therapy as a potential candidate for treating the sphingolipidoses

Science Translational Medicine

Volumn 8, Issue 355, 2016, Pages

  Kirkegaard, Thomas ^a   Gray, James ^b   Priestman, David A ^b   Wallom, Kerri Lee ^b   Atkins, Jennifer ^b   Olsen, Ole Dines ^a,c   Klein, Alexander ^d   Drndarski, Svetlana ^e   Petersen, Nikolaj H T ^a   Ingemann, Linda ^a   Smith, David A ^b   Morris, Lauren ^b   Bornæs, Claus ^a   Jørgensen, Signe Humle ^a   Williams, Ian ^b   Hinsby, Anders ^a   Arenz, Christoph ^d   Begley, David ^e   Jäättelä, Marja ^c   Platt, Frances M ^b  

^a ORPHAZYME A S   (Denmark)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c DANISH CANCER SOCIETY RESEARCH CENTER   (Denmark)

^d HUMBOLDT UNIVERSITY   (Germany)

^e KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA GALACTOSIDASE; ALPHA N ACETYLGALACTOSAMINIDASE; ARIMOCLOMOL; BETA N ACETYLHEXOSAMINIDASE A; BIS(MONOACYLGLYCERO)PHOSPHATE; CEREBROSIDE SULFATASE; DRUG ANTIBODY; GLOBOSIDE; GLYCEROPHOSPHATE; GLYCOSPHINGOLIPID; HEAT SHOCK PROTEIN 70; HEAT SHOCK TRANSCRIPTION FACTOR 1; LYSOSOME ENZYME; RECOMBINANT HEAT SHOCK PROTEIN 70; RECOMBINANT PROTEIN; SIALIDASE; UNCLASSIFIED DRUG; BONE MORPHOGENETIC PROTEIN; HEAT SHOCK PROTEIN; HYDROXYLAMINE; NPC1 PROTEIN, MOUSE; PROTEIN;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; BLOOD BRAIN BARRIER; CLINICAL ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG PENETRATION; DRUG TISSUE LEVEL; DRUG UPTAKE; FABRY DISEASE; FEMALE; FIBROBLAST; HUMAN; HUMAN CELL; LIPID STORAGE; LIPIDOSIS; LYSOSOME; MALE; MOUSE; MURINE MODEL; NEUROPROTECTION; NIEMANN PICK DISEASE; NONHUMAN; OPTIMAL DRUG DOSE; ORGAN DISTRIBUTION; PRIORITY JOURNAL; SANDHOFF DISEASE; TISSUE DISTRIBUTION; VOLUME OF DISTRIBUTION; ANIMAL; DISEASE EXACERBATION; DISEASE MODEL; DRUG EFFECTS; INTRAPERITONEAL DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; PATHOLOGY;

ADMINISTRATION, INTRAVENOUS; ANIMALS; BLOOD-BRAIN BARRIER; BONE MORPHOGENETIC PROTEINS; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; FABRY DISEASE; FIBROBLASTS; GLYCOSPHINGOLIPIDS; HEAT-SHOCK PROTEINS; HUMANS; HYDROXYLAMINES; INJECTIONS, INTRAPERITONEAL; LYSOSOMES; NIEMANN-PICK DISEASE, TYPE C; PROTEINS; RECOMBINANT PROTEINS; SPHINGOLIPIDOSES; TISSUE DISTRIBUTION;

EID: 84988869874     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aad9823     Document Type: Article

References (110)

1. G. Parenti, G. Andria, A. Ballabio, Lysosomal storage diseases: From pathophysiology to therapy. Annu. Rev. Med. 66, 471-486 (2015).
2. Y.-H. Xu, S. Barnes, Y. Sun, G. A. Grabowski, Multi-system disorders of glycosphingolipid and ganglioside metabolism. J. Lipid Res. 51, 1643-1675 (2010).
3. D. W. Neef, A. M. Jaeger, D. J. Thiele, Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nat. Rev. Drug Discov. 10, 930-944 (2011).
4. P. J. Muchowski, J. L. Wacker, Modulation of neurodegeneration by molecular chaperones. Nat. Rev. Neurosci. 6, 11-22 (2005).
5. D. Kieran, B. Kalmar, J. R. T. Dick, J. Riddoch-Contreras, G. Burnstock, L. Greensmith, Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Nat. Med. 10, 402-405 (2004).
6. T. Kirkegaard, A. G. Roth, N. H. T. Petersen, A. K. Mahalka, O. D. Olsen, I. Moilanen, A. Zylicz, J. Knudsen, K. Sandhoff, C. Arenz, P. K. J. Kinnunen, J. Nylandsted, M. Jäättelä, Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature 463, 549-553 (2010).
7. L. Vígh, P. N. Literáti, I. Horváth, Z. Török, G. Balogh, A. Glatz, E. Kovács, I. Boros, P. Ferdinándy, B. Parkas, L. Jaszlits, A. Jednákovits, L. Korányi, B. Maresca, Bimoclomol: A nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects. Nat. Med. 3, 1150-1154 (1997).
8. S. M. Gehrig, C. van der Poel, T. A. Sayer, J. D. Schertzer, D. C. Henstridge, J. E. Church, S. Lamon, A. P. Russell, K. E. Davies, M. A. Febbraio, G. S. Lynch, Hsp72 preserves muscle function and slows progression of severe muscular dystrophy. Nature 484, 394-398 (2012).
9. J. Nylandsted, M. Gyrd-Hansen, A. Danielewicz, N. Fehrenbacher, U. Lademann, M. Høyer-Hansen, E. Weber, G. Multhoff, M. Rohde, M. Jäättelä, Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J. Exp. Med. 200, 425-435 (2004).
10. J.-H. Hwang, J. K. Ryu, Y. B. Yoon, K. H. Lee, Y.-S. Park, J.-W. Kim, N. Kim, D. H. Lee, J. B. Jeong, J.-S. Seo, Y.-T. Kim, Spontaneous activation of pancreas trypsinogen in heat shock protein 70.1 knock-out mice. Pancreas 31, 332-336 (2005).
11. T. Kirkegaard, M. Jäättelä, Lysosomal involvement in cell death and cancer. Biochim. Biophys. Acta 1793, 746-754 (2009).
12. T. Kolter, K. Sandhoff, Principles of lysosomal membrane digestion: Stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids. Annu. Rev. Cell Dev. Biol. 21, 81-103 (2005).
13. A. K. Mahalka, T. Kirkegaard, L. T. I. Jukola, M. Jäättelä, P. K. J. Kinnunen, Human heat shock protein 70 (Hsp70) as a peripheral membrane protein. Biochim. Biophys. Acta 1838, 1344-1361 (2014).
14. S. Locatelli-Hoops, N. Remmel, R. Klingenstein, B. Breiden, M. Rossocha, M. Schoeniger, C. Koenigs, W. Saenger, K. Sandhoff, Saposin A mobilizes lipids from low cholesterol and high bis(monoacylglycerol)phosphate-containing membranes: Patient variant Saposin A lacks lipid extraction capacity. J. Biol. Chem. 281, 32451-32460 (2006).
15. G. Wilkening, T. Linke, K. Sandhoff, Lysosomal degradation on vesicular membrane surfaces. Enhanced glucosylceramide degradation by lysosomal anionic lipids and activators. J. Biol. Chem. 273, 30271-30278 (1998).
16. G. Wilkening, T. Linke, G. Uhlhorn-Dierks, K. Sandhoff, Degradation of membrane-bound ganglioside GM1. Stimulation by bis(monoacylglycero)phosphate and the activator proteins SAP-B and GM2-AP. J. Biol. Chem. 275, 35814-35819 (2000).
17. T. Linke, G. Wilkening, F. Sadeghlar, H. Mozcall, K. Bernardo, E. Schuchman, K. Sandhoff, Interfacial regulation of acid ceramidase activity. Stimulation of ceramide degradation by lysosomal lipids and sphingolipid activator proteins. J. Biol. Chem. 276, 5760-5768 (2001).
18. T. Linke, G. Wilkening, S. Lansmann, H. Moczall, O. Bartelsen, J. Weisgerber, K. Sandhoff, Stimulation of acid sphingomyelinase activity by lysosomal lipids and sphingolipid activator proteins. Biol. Chem. 382, 283-290 (2001).
19. N. H. T. Petersen, T. Kirkegaard, HSP70 and lysosomal storage disorders: Novel therapeutic opportunities. Biochem. Soc. Trans. 38, 1479-1483 (2010).
20. M. E. Guicciardi, M. Leist, G. J. Gores, Lysosomes in cell death. Oncogene 23, 2881-2890 (2004).
21. M. C. Micsenyi, J. Sikora, G. Stephney, K. Dobrenis, S. U. Walkley, Lysosomal membrane permeability stimulates protein aggregate formation in neurons of a lysosomal disease. J. Neurosci. 33, 10815-10827 (2013).
22. D. te Vruchte, A. O. Speak, K. L. Wallom, N. Al Eisa, D. A. Smith, C. J. Hendriksz, L. Simmons, R. H. Lachmann, A. Cousins, R. Hartung, E. Mengel, H. Runz, M. Beck, Y. Amraoui, J. Imrie, E. Jacklin, K. Riddick, N. M. Yanjanin, C. A. Wassif, A. Rolfs, F. Rimmele, N. Wright, C. Taylor, U. Ramaswami, T. M. Cox, C. Hastings, X. Jiang, R. Sidhu, D. S. Ory, B. Arias, M. Jeyakumar, D. J. Sillence, J. E. Wraith, F. D. Porter, M. Cortina-Borja, F. M. Platt, Relative acidic compartment volume as a lysosomal storage disorder-associated biomarker. J. Clin. Invest. 124, 1320-1328 (2014).
23. N. H. T. Petersen, O. D. Olsen, L. Groth-Pedersen, A.-M. Ellegaard, M. Bilgin, S. Redmer, M. S. Ostenfeld, D. Ulanet, T. H. Dovmark, A. Lønborg, S. D. Vindeløv, D. Hanahan, C. Arenz, C. S. Ejsing, T. Kirkegaard, M. Rohde, J. Nylandsted, M. Jäättelä, Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase. Cancer Cell 24, 379-393 (2013).
24. R. A. Nixon, The role of autophagy in neurodegenerative disease. Nat. Med. 19, 983-997 (2013).
25. M. S. Ostenfeld, M. Høyer-Hansen, L. Bastholm, N. Fehrenbacher, O. D. Olsen, L. Groth-Pedersen, P. Puustinen, T. Kirkegaard-Sorensen, J. Nylandsted, T. Farkas, M. Jäättelä, Anti-cancer agent siramesine is a lysosomotropic detergent that induces cytoprotective autophagosome accumulation. Autophagy 4, 487-499 (2008).
26. N. W. Werneburg, M. E. Guicciardi, S. F. Bronk, G. J. Gores, Tumor necrosis factor-a-associated lysosomal permeabilization is cathepsin B dependent. Am. J. Physiol. Gastrointest. Liver Physiol. 283, G947-G956 (2002).
27. T.-W. Mu, D. S. T. Ong, Y.-J. Wang, W. E. Balch, J. R. Yates III, L. Segatori, J. W. Kelly, Chemical and biological approaches synergize to ameliorate protein-folding diseases. Cell 134, 769-781 (2008).
28. H. Zhu, T. Yoshimoto, T. Yamashima, Heat shock protein 70.1 (Hsp70.1) affects neuronal cell fate by regulating lysosomal acid sphingomyelinase. J. Biol. Chem. 289, 27432-27443 (2014).
29. N. Nakasone, Y. S. Nakamura, K. Higaki, N. Oumi, K. Ohno, H. Ninomiya, Endoplasmic reticulumassociated degradation of Niemann-Pick C1: Evidence for the role of heat shock proteins and identification of lysine residues that accept ubiquitin. J. Biol. Chem. 289, 19714-19725 (2014).
30. C. Yang, C. L. Swallows, C. Zhang, J. Lu, H. Xiao, R. O. Brady, Z. Zhuang, Celastrol increases glucocerebrosidase activity in Gaucher disease by modulating molecular chaperones. Proc. Natl. Acad. Sci. U.S.A. 111, 249-254 (2014).
31. E. M. O'Leary, S. A. Igdoura, The therapeutic potential of pharmacological chaperones and proteosomal inhibitors, Celastrol and MG132 in the treatment of sialidosis. Mol. Genet. Metab. 107, 173-185 (2012).
32. S. Zampieri, B. Bembi, N. Rosso, M. Filocamo, A. Dardis, Treatment of human fibroblasts carrying NPC1 missense mutations with MG132 leads to an improvement of intracellular cholesterol trafficking. JIMD Rep. 2, 59-69 (2012).
33. L. Ingemann, T. Kirkegaard, Lysosomal storage diseases and the heat shock response: Convergences and therapeutic opportunities. J. Lipid Res. 55, 2198-2210 (2014).
34. M. E. Cudkowicz, J. M. Shefner, E. Simpson, D. Grasso, H. Yu, H. Zhang, A. Shui, D. Schoenfeld, R. H. Brown, S. Wieland, J. R. Barber, Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis. Muscle Nerve 38, 837-844 (2008).
35. V. Lanka, S. Wieland, J. Barber, M. Cudkowicz, Arimoclomol: A potential therapy under development for ALS. Expert Opin. Investig. Drugs 18, 1907-1918 (2009).
36. J. Anckar, L. Sistonen, Regulation of HSF1 function in the heat stress response: Implications in aging and disease. Annu. Rev. Biochem. 80, 1089-1115 (2011).
37. T. Crul, N. Toth, S. Piotto, P. Literati-Nagy, K. Tory, P. Haldimann, B. Kalmar, L. Greensmith, Z. Torok, G. Balogh, I. Gombos, F. Campana, S. Concilio, F. Gallyas, G. Nagy, Z. Berente, B. Gungor, M. Peter, A. Glatz, A. Hunya, Z. Literati-Nagy, L. Vigh, F. Hoogstra-Berends, A. Heeres, I. Kuipers, L. Loen, J.-P. Seerden, D. Zhang, R. A. M. Meijering, R. H. Henning, B. J. J. M. Brundel, H. H. Kampinga, L. Koranyi, Z. Szilvassy, J. Mandl, B. Sumegi, M. A. Febbraio, I. Horvath, P. L. Hooper, L. Vigh, Hydroximic acid derivatives: Pleiotropic HSP co-inducers restoring homeostasis and robustness. Curr. Pharm. Des. 19, 309-346 (2013).
38. D. A. Parfitt, M. Aguila, C. H. McCulley, D. Bevilacqua, H. F. Mendes, D. Athanasiou, S. S. Novoselov, N. Kanuga, P. M. Munro, P. J. Coffey, B. Kalmar, L. Greensmith, M. E. Cheetham, The heat-shock response co-inducer arimoclomol protects against retinal degeneration in rhodopsin retinitis pigmentosa. Cell Death Dis. 5, e1236 (2014).
39. E. Lloyd-Evans, A. J. Morgan, X. He, D. A. Smith, E. Elliot-Smith, D. J. Sillence, G. C. Churchill, E. H. Schuchman, A. Galione, F. M. Platt, Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat. Med. 14, 1247-1255 (2008).
40. C. Devlin, N. H. Pipalia, X. Liao, E. H. Schuchman, F. R. Maxfield, I. Tabas, Improvement in lipid and protein trafficking in Niemann-Pick C1 cells by correction of a secondary enzyme defect. Traffic 11, 601-615 (2010).
41. J. Chevallier, Z. Chamoun, G. Jiang, G. Prestwich, N. Sakai, S. Matile, R. G. Parton, J. Gruenberg, Lysobisphosphatidic acid controls endosomal cholesterol levels. J. Biol. Chem. 283, 27871-27880 (2008).
42. Y. Sugimoto, H. Ninomiya, Y. Ohsaki, K. Higaki, J. P. Davies, Y. A. Ioannou, K. Ohno, Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann-Pick C1-deficient cells. Proc. Natl. Acad. Sci. U.S.A. 98, 12391-12396 (2001).
43. M. Daugaard, M. Rohde, M. Jäättelä, The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions. FEBS Lett. 581, 3702-3710 (2007).
44. E. A. A. Nollen, R. I. Morimoto, Chaperoning signaling pathways: Molecular chaperones as stress-sensing 'heat shock' proteins. J. Cell Sci. 115, 2809-2816 (2002).
45. E. C. M. de Lange, P. G. M. Ravenstijn, D. Groenendaal, T. J. van Steeg, Toward the prediction of CNS drug-effect profiles in physiological and pathological conditions using microdialysis and mechanism-based pharmacokinetic-pharmacodynamic modeling. AAPS J. 7, E532-E543 (2005).
46. D. Triguero, J. Buciak, W. M. Pardridge, Capillary depletion method for quantification of blood-brain barrier transport of circulating peptides and plasma proteins. J. Neurochem. 54, 1882-1888 (1990).
47. C. S. Patlak, R. G. Blasberg, J. D. Fenstermacher, Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J. Cereb. Blood Flow Metab. 3, 1-7 (1983).
48. R. Gabathuler, Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases. Neurobiol. Dis. 37, 48-57 (2010).
49. S. Takemoto, M. Nishikawa, Y. Takakura, Pharmacokinetic and tissue distribution mechanism of mouse recombinant heat shock protein 70 in mice. Pharm. Res. 22, 419-426 (2005).
50. S. Basu, R. J. Binder, T. Ramalingam, P. K. Srivastava, CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14, 303-313 (2001).
51. T. Becker, F.-U. Hartl, F. Wieland, CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J. Cell Biol. 158, 1277-1285 (2002).
52. C. Gross, D. Hansch, R. Gastpar, G. Multhoff, Interaction of heat shock protein 70 peptide with NK cells involves the NK receptor CD94. Biol. Chem. 384, 267-279 (2003).
53. M. Demeule, J.-C. Currie, Y. Bertrand, C. Ché, T. Nguyen, A. Régina, R. Gabathuler, J.-P. Castaigne, R. Béliveau, Involvement of the low-density lipoprotein receptor-related protein in the transcytosis of the brain delivery vector angiopep-2. J. Neurochem. 106, 1534-1544 (2008).
54. T. Kirkegaard, Emerging therapies and therapeutic concepts for lysosomal storage diseases. Expert Opin. Orphan Drugs 1, 385-404 (2013).
55. P. G. Pentchev, A. D. Boothe, H. S. Kruth, H. Weintroub, J. Stivers, R. O. Brady, A genetic storage disorder in BALB/C mice with a metabolic block in esterification of exogenous cholesterol. J. Biol. Chem. 259, 5784-5791 (1984).
56. T. Ohshima, G. J. Murray, W. D. Swaim, G. Longenecker, J. M. Quirk, C. O. Cardarelli, Y. Sugimoto, I. Pastan, M. M. Gottesman, R. O. Brady, A. B. Kulkarni, a-Galactosidase A deficient mice: A model of Fabry disease. Proc. Natl. Acad. Sci. U.S.A. 94, 2540-2544 (1997).
57. K. Sango, S. Yamanaka, A. Hoffmann, Y. Okuda, A. Grinberg, H. Westphal, M. P. McDonald, J. N. Crawley, K. Sandhoff, K. Suzuki, R. L. Proia, Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism. Nat. Genet. 11, 170-176 (1995).
58. D. Phaneuf, N. Wakamatsu, J.-Q. Huang, A. Borowski, A. C. Peterson, S. R. Fortunato, G. Ritter, S. A. Igdoura, C. R. Morales, G. Benoit, B. R. Akerman, D. Leclerc, N. Hanai, J. D. Marth, J. M. Trasler, R. A. Gravel, Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases. Hum. Mol. Genet. 5, 1-14 (1996).
59. Y. A. Ioannou, K. M. Zeidner, R. E. Gordon, R. J. Desnick, Fabry disease: Preclinical studies demonstrate the effectiveness of a-galactosidase A replacement in enzyme-deficient mice. Am. J. Hum. Genet. 68, 14-25 (2001).
60. J. M. F. G. Aerts, W. W. Kallemeijn, W. Wegdam, M. Joao Ferraz, M. J. van Breemen, N. Dekker, G. Kramer, B. J. Poorthuis, J. E. M. Groener, J. Cox-Brinkman, S. M. Rombach, C. E. M. Hollak, G. E. Linthorst, M. D. Witte, H. Gold, G. A. van der Marel, H. S. Overkleeft, R. G. Boot, Biomarkers in the diagnosis of lysosomal storage disorders: Proteins, lipids, and inhibodies. J. Inherit. Metab. Dis. 34, 605-619 (2011).
61. A. Abe, S. Gregory, L. Lee, P. D. Killen, R. O. Brady, A. Kulkarni, J. A. Shayman, Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. J. Clin. Invest. 105, 1563-1571 (2000).
62. A. O. Speak, M. Salio, D. C. A. Neville, J. Fontaine, D. A. Priestman, N. Platt, T. Heare, T. D. Butters, R. A. Dwek, F. Trottein, M. A. Exley, V. Cerundolo, F. M. Platt, Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals. Proc. Natl. Acad. Sci. U.S.A. 104, 5971-5976 (2007).
63. M. Jeyakumar, T. D. Butters, M. Cortina-Borja, V. Hunnam, R. L. Proia, V. H. Perry, R. A. Dwek, F. M. Platt, Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin. Proc. Natl. Acad. Sci. U.S.A. 96, 6388-6393 (1999).
64. M. Zervas, K. L. Somers, M. A. Thrall, S. U. Walkley, Critical role for glycosphingolipids in Niemann-Pick disease type C. Curr. Biol. 11, 1283-1287 (2001).
65. M. T. Vanier, Niemann-Pick disease type C. Orphanet J. Rare Dis. 5, 16 (2010).
66. S. U. Walkley, M. T. Vanier, Secondary lipid accumulation in lysosomal disease. Biochim. Biophys. Acta 1793, 726-736 (2009).
67. G. Vaquer, F. Rivière Dannerstedt, M. Mavris, F. Bignami, J. Llinares-Garcia, K. Westermark, B. Sepodes, Animal models for metabolic, neuromuscular and ophthalmological rare diseases. Nat. Rev. Drug Discov. 12, 287-305 (2013).
68. M. Walterfang, M. Fahey, P. Desmond, A. Wood, M. L. Seal, C. Steward, C. Adamson, C. Kokkinos, M. Fietz, D. Velakoulis, White and gray matter alterations in adults with Niemann-Pick disease type C: A cross-sectional study. Neurology 75, 49-56 (2010).
69. T. Yu, A. P. Lieberman, Npc1 acting in neurons and glia is essential for the formation and maintenance of CNS myelin. PLOS Genet. 9, e1003462 (2013).
70. M. T. Vanier, Lipid changes in Niemann-Pick disease type C brain: Personal experience and review of the literature. Neurochem. Res. 24, 481-489 (1999).
71. S. Takikita, T. Fukuda, I. Mohri, T. Yagi, K. Suzuki, Perturbed myelination process of premyelinating oligodendrocyte in Niemann-Pick type C mouse. J. Neuropathol. Exp. Neurol. 63, 660-673 (2004).
72. M. Walterfang, M. D. Macfarlane, J. C. L. Looi, L. Abel, E. Bowman, M. C. Fahey, P. Desmond, D. Velakoulis, Pontine-to-midbrain ratio indexes ocular-motor function and illness stage in adult Niemann-Pick disease type C. Eur. J. Neurol. 19, 462-467 (2012).
73. M. Walterfang, M. Fahey, L. Abel, M. Fietz, A. Wood, E. Bowman, D. Reutens, D. Velakoulis, Size and shape of the corpus callosum in adult Niemann-Pick type C reflects state and trait illness variables. AJNR Am. J. Neuroradiol. 32, 1340-1346 (2011).
74. X. Yan, J. Lukas, M. Witt, A. Wree, R. Huäbner, M. Frech, R. Köhling, A. Rolfs, J. Luo, Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse. Metab. Brain Dis. 26, 299-306 (2011).
75. R. L. Schnaar, Brain gangliosides in axon-myelin stability and axon regeneration. FEBS Lett. 584, 1741-1747 (2010).
76. R. K. Yu, Y. Nakatani, M. Yanagisawa, The role of glycosphingolipid metabolism in the developing brain. J. Lipid Res. 50, S440-S445 (2009).
77. A. Tessitore, M. del P. Martin, R. Sano, Y. Ma, L. Mann, A. Ingrassia, E. D. Laywell, D. A. Steindler, L. M. Hendershot, A. d'Azzo, GM1-ganglioside-mediated activation of the unfolded protein response causes neuronal death in a neurodegenerative gangliosidosis. Mol. Cell 15, 753-766 (2004).
78. R. Sano, I. Annunziata, A. Patterson, S. Moshiach, E. Gomero, J. Opferman, M. Forte, A. d'Azzo, GM1-ganglioside accumulation at the mitochondria-associated ER membranes links ER stress to Ca2+-dependent mitochondrial apoptosis. Mol. Cell 36, 500-511 (2009).
79. B. Kalmar, C.-H. Lu, L. Greensmith, The role of heat shock proteins in amyotrophic lateral sclerosis: The therapeutic potential of arimoclomol. Pharmacol. Ther. 141, 40-54 (2014).
80. M. Benatar, J. Kurent, D. H. Moore, Treatment for familial amyotrophic lateral sclerosis/ motor neuron disease. Cochrane Database Syst. Rev. CD006153 (2009).
81. J. Macías-Vidal, M. Girós, M. Guerrero, P. Gascón, J. Serratosa, O. Bachs, M. J. Coll, The proteasome inhibitor bortezomib reduced cholesterol accumulation in fibroblasts from Niemann-Pick type C patients carrying missense mutations. FEBS J. 281, 4450-4466 (2014).
82. R. I. Morimoto, The heat shock response: Systems biology of proteotoxic stress in aging and disease. Cold Spring Harb. Symp. Quant. Biol. 76, 91-99 (2011).
83. B. Malik, N. Nirmalananthan, A. L. Gray, A. R. La Spada, M. G. Hanna, L. Greensmith, Co-induction of the heat shock response ameliorates disease progression in a mouse model of human spinal and bulbar muscular atrophy: Implications for therapy. Brain 136 (Pt. 3), 926-943 (2013).
84. C. Yang, S. Rahimpour, J. Lu, K. Pacak, B. Ikejiri, R. O. Brady, Z. Zhuang, Histone deacetylase inhibitors increase glucocerebrosidase activity in Gaucher disease by modulation of molecular chaperones. Proc. Natl. Acad. Sci. U.S.A. 110, 966-971 (2013).
85. R. I. Morimoto, Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Genes Dev. 22, 1427-1438 (2008).
86. M. Jäättelä, Heat shock proteins as cellular lifeguards. Ann. Med. 31, 261-271 (1999).
87. C. D. Davidson, N. F. Ali, M. C. Micsenyi, G. Stephney, S. Renault, K. Dobrenis, D. S. Ory, M. T. Vanier, S. U. Walkley, Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression. PLOS One 4, e6951 (2009).
88. V. M. Stein, A. Crooks, W. Ding, M. Prociuk, P. O'Donnell, C. Bryan, T. Sikora, J. Dingemanse, M. T. Vanier, S. U. Walkley, C. H. Vite, Miglustat improves Purkinje cell survival and alters microglial phenotype in feline Niemann-Pick disease type C. J. Neuropathol. Exp. Neurol. 71, 434-448 (2012).
89. J. B. Nietupski, J. J. Pacheco, W.-L. Chuang, K. Maratea, L. Li, J. Foley, K. M. Ashe, C. G. F. Cooper, J. M. F. G. Aerts, D. P. Copeland, R. K. Scheule, S. H. Cheng, J. Marshall, Iminosugar-based inhibitors of glucosylceramide synthase prolong survival but paradoxically increase brain glucosylceramide levels in Niemann-Pick C mice. Mol. Genet. Metab. 105, 621-628 (2012).
90. N. H. Pipalia, C. C. Cosner, A. Huang, A. Chatterjee, P. Bourbon, N. Farley, P. Helquist, O. Wiest, F. R. Maxfield, Histone deacetylase inhibitor treatment dramatically reduces cholesterol accumulation in Niemann-Pick type C1 mutant human fibroblasts. Proc. Natl. Acad. Sci. U.S.A. 108, 5620-5625 (2011).
91. K. J. Dean, C. C. Sweeley, Studies on human liver a-galactosidases. II. Purification and enzymatic properties of a-galactosidase B (a-N-acetylgalactosaminidase). J. Biol. Chem. 254, 10001-10005 (1979).
92. M. E. Gelsthorpe, N. Baumann, E. Millard, S. E. Gale, S. J. Langmade, J. E. Schaffer, D. S. Ory, Niemann-Pick type C1 I1061T mutant encodes a functional protein that is selected for endoplasmic reticulum-associated degradation due to protein misfolding. J. Biol. Chem. 283, 8229-8236 (2008).
93. E. Mengel, H.-H. Kluänemann, C. M. Lourenço, C. J. Hendriksz, F. Sedel, M. Walterfang, S. A. Kolb, Niemann-Pick disease type C symptomatology: An expert-based clinical description. Orphanet J. Rare Dis. 8, 166 (2013).
94. M. Praggastis, B. Tortelli, J. Zhang, H. Fujiwara, R. Sidhu, A. Chacko, Z. Chen, C. Chung, A. P. Lieberman, J. Sikora, C. Davidson, S. U. Walkley, N. H. Pipalia, F. R. Maxfield, J. E. Schaffer, D. S. Ory, A murine Niemann-Pick C1 I1061T knock-in model recapitulates the pathological features of the most prevalent human disease allele. J. Neurosci. 35, 8091-8106 (2015).
95. D. J. Gifondorwa, M. B. Robinson, C. D. Hayes, A. R. Taylor, D. M. Prevette, R. W. Oppenheim, J. Caress, C. E. Milligan, Exogenous delivery of heat shock protein 70 increases lifespan in a mouse model of amyotrophic lateral sclerosis. J. Neurosci. 27, 13173-13180 (2007).
96. J. C. Plumier, B. M. Ross, R. W. Currie, C. E. Angelidis, H. Kazlaris, G. Kollias, G. N. Pagoulatos, Transgenic mice expressing the human heat shock protein 70 have improved post-ischemic myocardial recovery. J. Clin. Invest. 95, 1854-1860 (1995).
97. M. S. Marber, R. Mestril, S. H. Chi, M. R. Sayen, D. M. Yellon, W. H. Dillmann, Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. J. Clin. Invest. 95, 1446-1456 (1995).
98. M. Ahmed, P. M. Machado, A. Miller, C. Spicer, L. Herbelin, J. He, J. Noel, Y. Wang, A. L. McVey, M. Pasnoor, P. Gallagher, J. Statland, C.-H. Lu, B. Kalmar, S. Brady, H. Sethi, G. Samandouras, M. Parton, J. L. Holton, A. Weston, L. Collinson, J. P. Taylor, G. Schiavo, M. G. Hanna, R. J. Barohn, M. M. Dimachkie, L. Greensmith, Targeting protein homeostasis in sporadic inclusion body myositis. Sci. Transl. Med. 8, 331ra41 (2016).
99. E. Lloyd-Evans, F. M. Platt, Lipids on trial: The search for the offending metabolite in Niemann-Pick type C disease. Traffic 11, 419-428 (2010).
100. F. M. Platt, Sphingolipid lysosomal storage disorders. Nature 510, 68-75 (2014).
101. A. Buchberger, B. Bukau, T. Sommer, Protein quality control in the cytosol and the endoplasmic reticulum: Brothers in arms. Mol. Cell 40, 238-252 (2010).
102. B. Kalmar, G. Burnstock, G. Vrbová, R. Urbanics, P. Csermely, L. Greensmith, Upregulation of heat shock proteins rescues motoneurones from axotomy-induced cell death in neonatal rats. Exp. Neurol. 176, 87-97 (2002).
103. M. Kuärthy, T. Mogyorósi, K. Nagy, T. Kukorelli, A. Jednákovits, L. Tálosi, K. Bíró, Effect of BRX-220 against peripheral neuropathy and insulin resistance in diabetic rat models. Ann. N. Y. Acad. Sci. 967, 482-489 (2002).
104. B. Kalmar, S. Novoselov, A. Gray, M. E. Cheetham, B. Margulis, L. Greensmith, Late stage treatment with arimoclomol delays disease progression and prevents protein aggregation in the SOD1G93A mouse model of ALS. J. Neurochem. 107, 339-350 (2008).
105. T. I. F. H. Cremers, G. Flik, C. Hofland, R. E. Stratford Jr., Microdialysis evaluation of clozapine and N-desmethylclozapine pharmacokinetics in rat brain. Drug Metab. Dispos. 40, 1909-1916 (2012).
106. D. J. Begley, D. G. Chain, Proceedings of the Physiological Society, 24-25 February 1984, Imperial College Meeting: Demonstrations. J. Physiol. 351, 1-8 (1984).
107. S. K. Loftus, J. A. Morris, E. D. Carstea, J. Z. Gu, C. Cummings, A. Brown, J. Ellison, K. Ohno, M. A. Rosenfeld, D. A. Tagle, P. G. Pentchev, W. J. Pavan, Murine model of Niemann-Pick C disease: Mutation in a cholesterol homeostasis gene. Science 277, 232-235 (1997).
108. D. C. A. Neville, V. Coquard, D. A. Priestman, D. J. M. te Vruchte, D. J. Sillence, R. A. Dwek, F. M. Platt, T. D. Butters, Analysis of fluorescently labeled glycosphingolipid-derived oligosaccharides following ceramide glycanase digestion and anthranilic acid labeling. Anal. Biochem. 331, 275-282 (2004).
109. J. Folch, M. Lees, G. H. Sloane Stanley, A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497-509 (1957).
110. E. Elliot-Smith, A. O. Speak, E. Lloyd-Evans, D. A. Smith, A. C. van der Spoel, M. Jeyakumar, T. D. Butters, R. A. Dwek, A. d'Azzo, F. M. Platt, Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. Mol. Genet. Metab. 94, 204-211 (2008).