Neuroinflammatory paradigms in lysosomal storage diseases

Frontiers in Neuroscience

Volumn 9, Issue OCT, 2015, Pages

  Bosch, Megan E ^a   Kielian, Tammy ^a  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

Astrocytes; Danger associated molecular patterns; Lysosomal storage disease; Microglia; Neuroinflammation

Indexed keywords

CHEMOKINE; CYTOKINE; GLUCOSYLCERAMIDASE; GLYCOSPHINGOLIPID; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 6; LIPID; PROTEIN; SPHINGOMYELIN PHOSPHODIESTERASE; TUMOR NECROSIS FACTOR ALPHA;

APOPTOSIS; ASTROCYTE; AUTOPHAGY; CENTRAL NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM DISEASE; CHRONIC INFLAMMATION; DISEASE DURATION; ENDOSOME; GAUCHER DISEASE; GENE MUTATION; GLIA CELL; HUMAN; INFLAMMATION; LYSOSOME; LYSOSOME STORAGE DISEASE; MACROMOLECULE; METABOLIC DISORDER; MICROGLIA; MITOSIS; MOUSE; MUCOPOLYSACCHARIDOSIS; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NEURONAL CEROID LIPOFUSCINOSIS; NEUROPROTECTION; NIEMANN PICK DISEASE; NONHUMAN; PATHOGENESIS; PHAGOCYTOSIS; PHAGOSOME; REVIEW;

EID: 84949679955     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2015.00417     Document Type: Review

References (125)

1. Alam, M. S., Getz, M., Yi, S., Kurkewich, J., Safeukui, I., and Haldar, K. (2014). Plasma signature of neurological disease in the monogenetic disorder Niemann-Pick Type, C. J. Biol. Chem. 289, 8051-8066. doi: 10.1074/jbc.M113.526392
2. Alliot, F., Godin, I., and Pessac, B. (1999). Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res. Dev. Brain Res. 117, 145-152. doi: 10.1016/S0165-3806(99)00113-3
3. Alobaidy, H. (2015). Recent advances in the diagnosis and treatment of niemann-pick disease type C in children: a guide to early diagnosis for the general pediatrician. Int. J. Pediatr. 2015:816593. doi: 10.1155/2015/816593
4. Alroy, J., Garganta, C., and Wiederschain, G. (2014). Secondary biochemical and morphological consequences in lysosomal storage diseases. Biochem. Biokhim. 79, 619-636. doi: 10.1134/S0006297914070049
5. Amor, S., Peferoen, L. A., Vogel, D. Y., Breur, M., van der Valk, P., Baker, D., et al. (2014). Inflammation in neurodegenerative diseases-an update. Immunology 142, 151-166. doi: 10.1111/imm.12233
6. Anderson, G. W., Goebel, H. H., and Simonati, A. (2013). Human pathology in NCL. Biochim. Biophys. Acta 1832, 1807-1826. doi: 10.1016/j.bbadis.2012.11.014
7. Appelqvist, H., Wäster, P., Kågedal, K., and öllinger, K. (2013). The lysosome: from waste bag to potential therapeutic target. J. Mol. Cell Biol. 5, 214-226. doi: 10.1093/jmcb/mjt022
8. Archer, L. D., Langford-Smith, K. J., Bigger, B. W., and Fildes, J. E. (2014). Mucopolysaccharide diseases: a complex interplay between neuroinflammation, microglial activation and adaptive immunity. J. Inherit. Metab. Dis. 37, 1-12. doi: 10.1007/s10545-013-9613-3
9. Arfi, A., Richard, M., Gandolphe, C., Bonnefont-Rousselot, D., Thérond, P., and Scherman, D. (2011). Neuroinflammatory and oxidative stress phenomena in MPS IIIA mouse model: the positive effect of long-term aspirin treatment. Mol. Genet. Metab. 103, 18-25. doi: 10.1016/j.ymgme.2011.01.015
10. Assous, M., Had-Aissouni, L., Gubellini, P., Melon, C., Nafia, I., Salin, P., et al. (2014). Progressive Parkinsonism by acute dysfunction of excitatory amino acid transporters in the rat substantia nigra. Neurobiol. Dis. 65, 69-81. doi: 10.1016/j.nbd.2014.01.011
11. Ballabio, A., and Gieselmann, V. (2009). Lysosomal disorders: from storage to cellular damage. Biochim. Biophys. Acta 1793, 684-696. doi: 10.1016/j.bbamcr.2008.12.001
12. Barak, V., Acker, M., Nisman, B., Kalickman, I., Abrahamov, A., Zimran, A., et al. (1999). Cytokines in Gaucher's disease. Eur. Cytokine Netw. 10, 205-210.
13. Baudry, M., Yao, Y., Simmons, D., Liu, J., and Bi, X. (2003). Postnatal development of inflammation in a murine model of Niemann-Pick type C disease: immunohistochemical observations of microglia and astroglia. Exp. Neurol. 184, 887-903. doi: 10.1016/S0014-4886(03)00345-5
14. Bennett, L. L., and Mohan, D. (2013). Gaucher disease and its treatment options. Ann. Pharmacother. 47, 1182-1193. doi: 10.1177/1060028013500469
15. Bergsbaken, T., Fink, S. L., and Cookson, B. T. (2009). Pyroptosis: host cell death and inflammation. Nat. Rev. Microbiol. 7, 99-109. doi: 10.1038/nrmicro2070
16. Bettman, N., Avivi, I., Rosenbaum, H., Bisharat, L., and Katz, T. (2015). Impaired migration capacity in monocytes derived from patients with Gaucher disease. Blood Cells Mol. Dis. 55, 180-186. doi: 10.1016/j.bcmd.2014.12.003
17. Boustany, R. M. (2013). Lysosomal storage diseases-the horizon expands. Nat. Rev. Neurol. 9, 583-598. doi: 10.1038/nrneurol.2013.163
18. Bronson, R. T., Lake, B. D., Cook, S., Taylor, S., and Davisson, M. T. (1993). Motor neuron degeneration of mice is a model of neuronal ceroid lipofuscinosis (Batten's disease). Ann. Neurol. 33, 381-385. doi: 10.1002/ana.410330408
19. Brunkhorst, R., Vutukuri, R., and Pfeilschifter, W. (2014). Fingolimod for the treatment of neurological diseases-state of play and future perspectives. Front. Cell. Neurosci. 8:283. doi: 10.3389/fncel.2014.00283
20. Burkovetskaya, M., Karpuk, N., Xiong, J., Bosch, M., Boska, M., Takeuchi, H. Kielian, T., et al. (2014). Evidence for aberrant astrocyte hemichannel activity in Juvenile Neuronal Ceroid Lipofuscinosis (JNCL). PLoS ONE 9:e95023. doi: 10.1371/journal.pone.0095023
21. Camargo, F., Erickson, R. P., Garver, W. S., Hossain, G. S., Carbone, P. N., Heidenreich, R. A., et al. (2001). Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease. Life Sci. 70, 131-142. doi: 10.1016/S0024-3205(01)01384-4
22. Campos, D., and Monaga, M. (2012). Mucopolysaccharidosis type I: current knowledge on its pathophysiological mechanisms. Metab. Brain Dis. 27, 121-129. doi: 10.1007/s11011-012-9302-1
23. Cooper, G. M. (ed.). (2000). "Structure of the plasma membrane," in The Cell: A Molecular Approach Sunderland (MA): Sinauer Associates (Sunderland: Sinauer Associates), 235-321.
24. Cooper, J. D. (2003). Progress towards understanding the neurobiology of Batten disease or neuronal ceroid lipofuscinosis. Curr. Opin. Neurol. 16, 121-128. doi: 10.1097/00019052-200304000-00001
25. Cotman, S. L., and Staropoli, J. F. (2012). The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking. Clin. Lipidol. 7, 79-91. doi: 10.2217/clp.11.70
26. Cotman, S. L., Vrbanac, V., Lebel, L. A., Lee, R. L., Johnson, K. A., Donahue, L. R., et al. (2002). Cln3(Deltaex7/8) knock-in mice with the common JNCL mutation exhibit progressive neurologic disease that begins before birth. Hum. Mol. Genet. 11, 2709-2721. doi: 10.1093/hmg/11.22.2709
27. Cox, T. M., and Cachón-González, M. B. (2012). The cellular pathology of lysosomal diseases. J. Pathol. 226, 241-254. doi: 10.1002/path.3021
28. Davies, L., Fassbender, K., and Walter, S. (2013). Sphingolipids in neuroinflammation. Handb. Exp. Pharmacol. 216, 421-430. doi: 10.1007/978-3-7091-1511-4_21
29. de Duve, C. (1969). The peroxisome: a new cytoplasmic organelle. Proc. R. Soc. Lond. Ser. B. Biol. Sci. 173, 71-83. doi: 10.1098/rspb.1969.0039
30. De Francesco, P. N., Mucci, J. M., Ceci, R., Fossati, C. A., and Rozenfeld, P. A. (2013). Fabry disease peripheral blood immune cells release inflammatory cytokines: role of globotriaosylceramide. Mol. Genet. Metab. 109, 93-99. doi: 10.1016/j.ymgme.2013.02.003
31. Dheen, S. T., Kaur, C., and Ling, E. A. (2007). Microglial activation and its implications in the brain diseases. Curr. Med. Chem. 14, 1189-1197. doi: 10.2174/092986707780597961
32. DiRosario, J., Divers, E., Wang, C., Etter, J., Charrier, A., Jukkola, P., et al. (2009). Innate and adaptive immune activation in the brain of MPS IIIB mouse model. J. Neurosci. Res. 87, 978-990. doi: 10.1002/jnr.21912
33. Dolisca, S. B., Mehta, M., Pearce, D. A., Mink, J. W., and Maria, B. L. (2013). Batten disease: clinical aspects, molecular mechanisms, translational science, and future directions. J. Child Neurol. 28, 1074-1100. doi: 10.1177/0883073813493665
34. Dong, Y., and Benveniste, E. N. (2001). Immune function of astrocytes. Glia 36, 180-190. doi: 10.1002/glia.1107
35. Doyle, K. M., Kennedy, D., Gorman, A. M., Gupta, S., Healy, S. J., and Samali, A. (2011). Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders. J. Cell. Mol. Med. 15, 2025-2039. doi: 10.1111/j.1582-4934.2011.01374.x
36. Enquist, I. B., Lo Bianco, C., Ooka, A., Nilsson, E., Månsson, J. E., Ehinger, M., et al. (2007). Murine models of acute neuronopathic Gaucher disease. Proc. Natl. Acad. Sci. U.S.A. 104, 17483-17488. doi: 10.1073/pnas.0708086104
37. Escolar, M. L., Poe, M. D., Provenzale, J. M., Richards, K. C., Allison, J., Wood, S., et al. (2005). Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N. Engl. J. Med. 352, 2069-2081. doi: 10.1056/NEJMoa042604
38. Farfel-Becker, T., Vitner, E. B., Pressey, S. N., Eilam, R., Cooper, J. D., and Futerman, A. H. (2011). Spatial and temporal correlation between neuron loss and neuroinflammation in a mouse model of neuronopathic Gaucher disease. Hum. Mol. Genet. 20, 1375-1386. doi: 10.1093/hmg/ddr019
39. Farina, C., Aloisi, F., and Meinl, E. (2007). Astrocytes are active players in cerebral innate immunity. Trends Immunol. 28, 138-145. doi: 10.1016/j.it.2007.01.005
40. Farooqui, A. A. (2009). Lipid mediators in the neural cell nucleus: their metabolism, signaling, and association with neurological disorders. Neuroscientist 15, 392-407. doi: 10.1177/1073858409337035
41. Fernandes-Alnemri, T., Yu, J. W., Datta, P., Wu, J., and Alnemri, E. S. (2009). AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458, 509-513. doi: 10.1038/nature07710
42. Finn, R., Kovacs, A. D., and Pearce, D. A. (2011). Altered sensitivity of cerebellar granule cells to glutamate receptor overactivation in the Cln3(Deltaex7/8)-knock-in mouse model of juvenile neuronal ceroid lipofuscinosis. Neurochem. Int. 58, 648-655. doi: 10.1016/j.neuint.2011.02.003
43. Futerman, A. H., and van Meer, G. (2004). The cell biology of lysosomal storage disorders. Nat. Rev. Mol. Cell Biol. 5, 554-565. doi: 10.1038/nrm1423
44. Gallala, H. D., Breiden, B., and Sandhoff, K. (2011). Regulation of the NPC2 protein-mediated cholesterol trafficking by membrane lipids. J. Neurochem. 116, 702-707. doi: 10.1111/j.1471-4159.2010.07014.x
45. Hachiya, Y., Hayashi, M., Kumada, S., Uchiyama, A., Tsuchiya, K., and Kurata, K. (2006). Mechanisms of neurodegeneration in neuronal ceroid-lipofuscinoses. Acta Neuropathol. 111, 168-177. doi: 10.1007/s00401-005-0024-x
46. Haltia, M. (2003). The neuronal ceroid-lipofuscinoses. J. Neuropathol. Exp. Neurol. 62, 1-13.
47. Hanke, M. L., and Kielian, T. (2011). Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin. Sci. 121, 367-387. doi: 10.1042/CS20110164
48. Hawkins-Salsbury, J. A., Cooper, J. D., and Sands, M. S. (2013). Pathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease). Biochim. Biophys. Acta 1832, 1906-1909. doi: 10.1016/j.bbadis.2013.05.026
49. Hawkins-Salsbury, J. A., Reddy, A. S., and Sands, M. S. (2011). Combination therapies for lysosomal storage disease: is the whole greater than the sum of its parts? Hum. Mol. Genet. 20, R54-R60. doi: 10.1093/hmg/ddr112
50. Hawkins-Salsbury, J. A., Shea, L., Jiang, X., Hunter, D. A., Guzman, A. M., Reddy, A. S., et al. (2015). Mechanism-based combination treatment dramatically increases therapeutic efficacy in murine globoid cell leukodystrophy. J. Neurosci. 35, 6495-6505. doi: 10.1523/JNEUROSCI.4199-14.2015
51. Hayase, T., Shimizu, J., Goto, T., Nozaki, Y., Mori, M., Takahashi, N., et al. (2010). Unilaterally and rapidly progressing white matter lesion and elevated cytokines in a patient with Tay-Sachs disease. Brain Dev. 32, 244-247. doi: 10.1016/j.braindev.2009.01.007
52. Haydon, P. G., and Nedergaard, M. (2015). How do astrocytes participate in neural plasticity? Cold Spring Harb. Perspect. Biol. 7:a020438. doi: 10.1101/cshperspect.a020438
53. Heneka, M. T., Carson, M. J., El Khoury, J., Landreth, G. E., Brosseron, F., Feinstein, D. L., et al. (2015). Neuroinflammation in Alzheimer's disease. Lancet Neurol. 14, 388-405. doi: 10.1016/S1474-4422(15)70016-5
54. Hong, Y. B., Kim, E. Y., and Jung, S. C. (2006). Upregulation of proinflammatory cytokines in the fetal brain of the Gaucher mouse. J. Korean Med. Sci. 21, 733-738. doi: 10.3346/jkms.2006.21.4.733
55. Huang, X., Suyama, K., Buchanan, J., Zhu, A. J., and Scott, M. P. (2005). A Drosophila model of the Niemann-Pick type C lysosome storage disease: dnpc1a is required for molting and sterol homeostasis. Development 132, 5115-5124. doi: 10.1242/dev.02079
56. Jalanko, A., and Braulke, T. (2009). Neuronal ceroid lipofuscinoses. Biochim. Biophys. Acta 1793, 697-709. doi: 10.1016/j.bbamcr.2008.11.004
57. Jeyakumar, M., Thomas, R., Elliot-Smith, E., Smith, D. A., van der Spoel, A. C., d'Azzo, A., et al. (2003). Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain 126, 974-987. doi: 10.1093/brain/awg089
58. Karpuk, N., Burkovetskaya, M., Fritz, T., Angle, A., and Kielian, T. (2011). Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity. J. Neurosci. 31, 414-425. doi: 10.1523/JNEUROSCI.5247-10.2011
59. Kielar, C., Maddox, L., Bible, E., Pontikis, C. C., Macauley, S. L., Griffey, M. A., et al. (2007). Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis. Neurobiol. Dis. 25, 150-162. doi: 10.1016/j.nbd.2006.09.001
60. Kollmann, K., Uusi-Rauva, K., Scifo, E., Tyynelä, J., Jalanko, A., and Braulke, T. (2013). Cell biology and function of neuronal ceroid lipofuscinosis-related proteins. Biochim. Biophys. Acta 1832, 1866-1881. doi: 10.1016/j.bbadis.2013.01.019
61. Korkotian, E., Schwarz, A., Pelled, D., Schwarzmann, G., Segal, M., and Futerman, A. H. (1999). Elevation of intracellular glucosylceramide levels results in an increase in endoplasmic reticulum density and in functional calcium stores in cultured neurons. J. Biol. Chem. 274, 21673-21678. doi: 10.1074/jbc.274.31.21673
62. Kulijewicz-Nawrot, M., Sykova, E., Chvatal, A., Verkhratsky, A., and Rodriguez, J. J. (2013). Astrocytes and glutamate homoeostasis in Alzheimer's disease: a decrease in glutamine synthetase, but not in glutamate transporter-1, in the prefrontal cortex. ASN Neuro 5, 273-282. doi: 10.1042/AN20130017
63. Lee, K. M., and MacLean, A. G. (2015). New advances on glial activation in health and disease. World J. Virol. 4, 42-55. doi: 10.5501/wjv.v4.i2.42
64. Lerner, T. J., Boustany, R.-M. N., Anderson, J. W., D'Arigo, K. L., Schlumpf, K., Buckler, A. J., et al. (1995). Isolation of a novel gene underlying Batten disease, CLN3. The International Batten Disease Consortium. Cell 82, 949-957. doi: 10.1016/0092-8674(95)90274-0
65. Lim, M. J., Beake, J., Bible, E., Curran, T. M., Ramirez-Montealegre, D., Pearce, D. A., et al. (2006). Distinct patterns of serum immunoreactivity as evidence for multiple brain-directed autoantibodies in juvenile neuronal ceroid lipofuscinosis. Neuropathol. Appl. Neurobiol. 32, 469-482. doi: 10.1111/j.1365-2990.2006.00738.x
66. Lyman, M., Lloyd, D. G., Ji, X., Vizcaychipi, M. P., and Ma, D. (2014). Neuroinflammation: the role and consequences. Neurosci. Res. 79, 1-12. doi: 10.1016/j.neures.2013.10.004
67. Macauley, S. L., Roberts, M. S., Wong, A. M., McSloy, F., Reddy, A. S., Cooper, J. D., et al. (2012). Synergistic effects of central nervous system-directed gene therapy and bone marrow transplantation in the murine model of infantile neuronal ceroid lipofuscinosis. Ann. Neurol. 71, 797-804. doi: 10.1002/ana.23545
68. Mauhin, W., Lidove, O., Masat, E., Mingozzi, F., Mariampillai, K., Ziza, J. M., et al. (2015). Innate and adaptive immune response in fabry disease. JIMD Rep. 22, 1-10. doi: 10.1007/8904_2014_371
69. Meares, G. P., Liu, Y., Rajbhandari, R., Qin, H., Nozell, S. E., Mobley, J. A., et al. (2014). PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum stress-induced inflammation. Mol. Cell. Biol. 34, 3911-3925. doi: 10.1128/MCB.00980-14
70. Meikle, P. J., Hopwood, J. J., Clague, A. E., and Carey, W. F. (1999). Prevalence of lysosomal storage disorders. JAMA 281, 249-254. doi: 10.1001/jama.281.3.249
71. Mencarelli, C., and Martinez-Martinez, P. (2013). Ceramide function in the brain: when a slight tilt is enough. Cell. Mol. Life Sci. 70, 181-203. doi: 10.1007/s00018-012-1038-x
72. Minghetti, L., and Levi, G. (1998). Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Progress Neurobiol. 54, 99-125. doi: 10.1016/S0301-0082(97)00052-X
73. Mitchison, H. M., Lim, M. J., and Cooper, J. D. (2004). Selectivity and types of cell death in the neuronal ceroid lipofuscinoses. Brain Pathol. 14, 86-96. doi: 10.1111/j.1750-3639.2004.tb00502.x
74. Mole, S. E., Williams, R. E., and Goebel, H. H. (2005). Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics 6, 107-126. doi: 10.1007/s10048-005-0218-3
75. Muenzer, J. (2004). The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J. Pediatr. 144, S27-S34. doi: 10.1016/j.jpeds.2004.01.052
76. Nair, S., Boddupalli, C. S., Verma, R., Liu, J., Yang, R., Pastores, G. M., et al. (2015). Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation. Blood 125, 1256-1271. doi: 10.1182/blood-2014-09-600270
77. Nixon, G. F. (2009). Sphingolipids in inflammation: pathological implications and potential therapeutic targets. Br. J. Pharmacol. 158, 982-993. doi: 10.1111/j.1476-5381.2009.00281.x
78. Orellana, J. A., Shoji, K. F., Abudara, V., Ezan, P., Amigou, E., Sáez, P. J., et al. (2011). Amyloid beta-induced death in neurons involves glial and neuronal hemichannels. J. Neurosci. 31, 4962-4977. doi: 10.1523/JNEUROSCI.6417-10.2011
79. Pahl, H. L., and Baeuerle, P. A. (1997). The ER-overload response: activation of NF-kappa B. Trends Biochem. Sci. 22, 63-67. doi: 10.1016/S0968-0004(96)10073-6
80. Palmer, D. N., Barry, L. A., Tyynelä, J., and Cooper, J. D. (2013). NCL disease mechanisms. Biochim. Biophys. Acta 1832, 1882-1893. doi: 10.1016/j.bbadis.2013.05.014
81. Park, I. H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., et al. (2008). Disease-specific induced pluripotent stem cells. Cell 134, 877-886. doi: 10.1016/j.cell.2008.07.041
82. Peake, K. B., Campenot, R. B., Vance, D. E., and Vance, J. E. (2011). Niemann-Pick Type C1 deficiency in microglia does not cause neuron death in vitro. Biochim. Biophys. Acta 1812, 1121-1129. doi: 10.1016/j.bbadis.2011.06.003
83. Pearce, D. A., Ferea, T., Nosel, S. A., Das, B., and Sherman, F. (1999). Action of BTN1, the yeast orthologue of the gene mutated in Batten disease. Nat. Genet. 22, 55-58. doi: 10.1038/8861
84. Pears, M. R., Cooper, J. D., Mitchison, H. M., Mortishire-Smith, R. J., Pearce, D. A., and Griffin, J. L. (2005). High resolution 1H NMR-based metabolomics indicates a neurotransmitter cycling deficit in cerebral tissue from a mouse model of Batten disease. J. Biol. Chem. 280, 42508-42514. doi: 10.1074/jbc.M507380200
85. Pears, M. R., Salek, R. M., Palmer, D. N., Kay, G. W., Mortishire-Smith, R. J., and Griffin, J. L. (2007). Metabolomic investigation of CLN6 neuronal ceroid lipofuscinosis in affected South Hampshire sheep. J. Neurosci. Res. 85, 3494-3504. doi: 10.1002/jnr.21343
86. Pereira, V. G., Gazarini, M. L., Rodrigues, L. C., da Silva, F. H., Han, S. W., Martins, A. M., et al. (2010). Evidence of lysosomal membrane permeabilization in mucopolysaccharidosis type I: rupture of calcium and proton homeostasis. J. Cell. Physiol. 223, 335-342. doi: 10.1002/jcp.22039
87. Persaud-Sawin, D. A., VanDongen, A., and Boustany, R. M. (2002). Motifs within the CLN3 protein: modulation of cell growth rates and apoptosis. Hum. Mol. Genet. 11, 2129-2142. doi: 10.1093/hmg/11.18.2129
88. Platt, F. M., Boland, B., and van der Spoel, A. C. (2012). The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction. J. Cell Biol. 199, 723-734. doi: 10.1083/jcb.201208152
89. Pontikis, C. C., Cella, C. V., Parihar, N., Lim, M. J., Chakrabarti, S., Mitchison, H. M., et al. (2004). Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation. Brain Res. 1023, 231-242. doi: 10.1016/j.brainres.2004.07.030
90. Pressey, S. N., Smith, D. A., Wong, A. M., Platt, F. M., and Cooper, J. D. (2012). Early glial activation, synaptic changes and axonal pathology in the thalamocortical system of Niemann-Pick type C1 mice. Neurobiol. Dis. 45, 1086-1100. doi: 10.1016/j.nbd.2011.12.027
91. Puranam, K., Qian, W. H., Nikbakht, K., Venable, M., Obeid, L., Hannun, Y., et al. (1997). Upregulation of Bcl-2 and elevation of ceramide in Batten disease. Neuropediatrics 28, 37-41. doi: 10.1055/s-2007-973664
92. Qin, E. Y., Hawkins-Salsbury, J. A., Jiang, X., Reddy, A. S., Farber, N. B., Ory, D. S., et al. (2012). Bone marrow transplantation increases efficacy of central nervous system-directed enzyme replacement therapy in the murine model of globoid cell leukodystrophy. Mol. Genet. Metab. 107, 186-196. doi: 10.1016/j.ymgme.2012.05.021
93. Rama Rao, K. V., and Kielian, T. (2015). Astrocytes and lysosomal storage diseases. Neuroscience. doi: 10.1016/j.neuroscience.2015.05.061. [Epub ahead of print].
94. Rock, R. B., Gekker, G., Hu, S., Sheng, W. S., Cheeran, M., Lokensgard, J. R., et al. (2004). Role of microglia in central nervous system infections. Clin. Microbiol. Rev. 17, 942-964. doi: 10.1128/CMR.17.4.942-964.2004
95. Rosenbaum, A. I., and Maxfield, F. R. (2011). Niemann-Pick type C disease: molecular mechanisms and potential therapeutic approaches. J. Neurochem. 116, 789-795. doi: 10.1111/j.1471-4159.2010.06976.x
96. Salminen, A., Kauppinen, A., Suuronen, T., Kaarniranta, K., and Ojala, J. (2009). ER stress in Alzheimer's disease: a novel neuronal trigger for inflammation and Alzheimer's pathology. J. Neuroinflammation 6:41. doi: 10.1186/1742-2094-6-41
97. Sama, D. M., and Norris, C. M. (2013). Calcium dysregulation and neuroinflammation: discrete and integrated mechanisms for age-related synaptic dysfunction. Ageing Res. Rev. 12, 982-995. doi: 10.1016/j.arr.2013.05.008
98. Santorelli, F. M., Garavaglia, B., Cardona, F., Nardocci, N., Bernardina, B. D., Sartori, S., et al. (2013). Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy. Orphanet J. Rare Dis. 8:19. doi: 10.1186/1750-1172-8-19
99. Sidransky, E., Fartasch, M., Lee, R. E., Metlay, L. A., Abella, S., Zimran, A., et al. (1996). Epidermal abnormalities may distinguish type 2 from type 1 and type 3 of Gaucher disease. Pediatr. Res. 39, 134-141. doi: 10.1203/00006450-199601000-00020
100. Sitter, B., Autti, T., Tyynela, J., Sonnewald, U., Bathen, T. F., Puranen, J., et al. (2004). High-resolution magic angle spinning and 1H magnetic resonance spectroscopy reveal significantly altered neuronal metabolite profiles in CLN1 but not in CLN3. J. Neurosci. Res. 77, 762-769. doi: 10.1002/jnr.20123
101. Smith, D., Wallom, K. L., Williams, I. M., Jeyakumar, M., and Platt, F. M. (2009). Beneficial effects of anti-inflammatory therapy in a mouse model of Niemann-Pick disease type C1. Neurobiol. Dis. 36, 242-251. doi: 10.1016/j.nbd.2009.07.010
102. Thundyil, J., and Lim, K. L. (2014). DAMPs and Neurodegeneration. Ageing Res. Rev. doi: 10.1016/j.arr.2014.11.003. [Epub ahead of print].
103. Tschopp, J., and Schroder, K. (2010). NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat. Rev. Immunol. 10, 210-215. doi: 10.1038/nri2725
104. Tuxworth, R. I., Chen, H., Vivancos, V., Carvajal, N., Huang, X., and Tear, G. (2011). The Batten disease gene CLN3 is required for the response to oxidative stress. Hum. Mol. Genet. 20, 2037-2047. doi: 10.1093/hmg/ddr088
105. Tybulewicz, V. L., Tremblay, M. L., LaMarca, M. E., Willemsen, R., Stubblefield, B. K., Winfield, S., et al. (1992). Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene. Nature 357, 407-410. doi: 10.1038/357407a0
106. Utz, J. R., Crutcher, T., Schneider, J., Sorgen, P., and Whitley, C. B. (2015). Biomarkers of central nervous system inflammation in infantile and juvenile gangliosidoses. Mol. Genet. Metab. 114, 274-280. doi: 10.1016/j.ymgme.2014.11.015
107. van der Hel, W. S., Notenboom, R. G., Bos, I. W., van Rijen, P. C., van Veelen, C. W., and de Graan, P. N. (2005). Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy. Neurology 64, 326-333. doi: 10.1212/01.WNL.0000149636.44660.99
108. Vanier, M. T. (2010). Niemann-Pick disease type C. Orphanet J. Rare Dis. 5:16. doi: 10.1186/1750-1172-5-16
109. Verkhratsky, A., Nedergaard, M., and Hertz, L. (2015). Why are astrocytes important? Neurochem. Res. 40, 389-401. doi: 10.1007/s11064-014-1403-2
110. Verkhratsky, A., and Parpura, V. (2015). Astrogliopathology in neurological, neurodevelopmental and psychiatric disorders. Neurobiol. Dis. doi: 10.1016/j.nbd.2015.03.025. [Epub ahead of print].
111. Vezzani, A., and Viviani, B. (2015). Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability. Neuropharmacology 96, 70-82. doi: 10.1016/j.neuropharm.2014.10.027
112. Villani, G. R., Gargiulo, N., Faraonio, R., Castaldo, S., Gonzalez, Y. R. E., and Di Natale, P. (2007). Cytokines, neurotrophins, and oxidative stress in brain disease from mucopolysaccharidosis IIIB. J. Neurosci. Res. 85, 612-622. doi: 10.1002/jnr.21134
113. Vite, C. H., Bagel, J. H., Swain, G. P., Prociuk, M., Sikora, T. U., Stein, V. M., et al. (2015). Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease. Sci. Transl. Med. 7, 276ra226. doi: 10.1126/scitranslmed.3010101
114. Vitner, E. B., Farfel-Becker, T., Eilam, R., Biton, I., and Futerman, A. H. (2012). Contribution of brain inflammation to neuronal cell death in neuronopathic forms of Gaucher's disease. Brain 135, 1724-1735. doi: 10.1093/brain/aws095
115. Vitner, E. B., and Futerman, A. H. (2013). Neuronal forms of Gaucher disease. Handb. Exp. Pharmacol. 216, 405-419. doi: 10.1007/978-3-7091-1511-4_20
116. Vitner, E. B., Futerman, A. H., and Platt, N. (2015). Innate immune responses in the brain of sphingolipid lysosomal storage diseases. Biol. Chem. 396, 659-667. doi: 10.1515/hsz-2014-0301
117. Vitner, E. B., Platt, F. M., and Futerman, A. H. (2010). Common and uncommon pathogenic cascades in lysosomal storage diseases. J. Biol. Chem. 285, 20423-20427. doi: 10.1074/jbc.R110.134452
118. Wang, M. L., Motamed, M., Infante, R. E., Abi-Mosleh, L., Kwon, H. J., Brown, M. S., et al. (2010). Identification of surface residues on Niemann-Pick C2 essential for hydrophobic handoff of cholesterol to NPC1 in lysosomes. Cell Metab. 12, 166-173. doi: 10.1016/j.cmet.2010.05.016
119. Wilkinson, F. L., Holley, R. J., Langford-Smith, K. J., Badrinath, S., Liao, A., Langford-Smith, A., et al. (2012). Neuropathology in mouse models of mucopolysaccharidosis type I, IIIA and IIIB. PLoS ONE 7:e35787. doi: 10.1371/journal.pone.0035787
120. Williams, I. M., Wallom, K. L., Smith, D. A., Al Eisa, N., Smith, C., and Platt, F. M. (2014). Improved neuroprotection using miglustat, curcumin and ibuprofen as a triple combination therapy in Niemann-Pick disease type C1 mice. Neurobiol. Dis. 67, 9-17. doi: 10.1016/j.nbd.2014.03.001
121. Williams, R. E., Aberg, L., Autti, T., Goebel, H. H., Kohlschütter, A., and Lönnqvist, T. (2006). Diagnosis of the neuronal ceroid lipofuscinoses: an update. Biochim. Biophys. Acta 1762, 865-872. doi: 10.1016/j.bbadis.2006.07.001
122. Wolf, D. A., Banerjee, S., Hackett, P. B., Whitley, C. B., McIvor, R. S., and Low, W. C. (2015). Gene therapy for neurologic manifestations of mucopolysaccharidoses. Expert Opin. Drug Deliv. 12, 283-296. doi: 10.1517/17425247.2015.966682
123. Wraith, J. E. (1995). The mucopolysaccharidoses: a clinical review and guide to management. Arch. Dis. Child. 72, 263-267. doi: 10.1136/adc.72.3.263
124. Xiong, J., and Kielian, T. (2013). Microglia in juvenile neuronal ceroid lipofuscinosis are primed toward a pro-inflammatory phenotype. J. Neurochem. 127, 245-258. doi: 10.1111/jnc.12385
125. Zündorf, G., and Reiser, G. (2011). Calcium dysregulation and homeostasis of neural calcium in the molecular mechanisms of neurodegenerative diseases provide multiple targets for neuroprotection. Antioxid. Redox Signal. 14, 1275-1288. doi: 10.1089/ars.2010.3359