NCL disease mechanisms

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1832, Issue 11, 2013, Pages 1882-1893

  Palmer, David N ^a   Barry, Lucy A ^a   Tyynelä, Jaana ^b   Cooper, Jonathan D ^c  

^a LINCOLN UNIVERSITY   (New Zealand)

^b UNIVERSITY OF HELSINKI   (Finland)

^c KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Biochemical abnormalities; Glial activation; Pathogenesis; Selective neuron loss; Storage material accumulation; Synaptic pathology

Indexed keywords

4 AMINOBUTYRIC ACID; INTERLEUKIN 1BETA; INTERLEUKIN 6; LYSOSOME ENZYME; MONOCYTE CHEMOTACTIC PROTEIN 1; PALMITOYL PROTEIN THIOESTERASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; SOMATOMEDIN B RECEPTOR; SPHINGOLIPID ACTIVATOR PROTEIN; TUMOR NECROSIS FACTOR ALPHA;

ADAPTIVE IMMUNITY; APOPTOSIS; AUTOPHAGY; BLOOD BRAIN BARRIER; CHOLESTEROL METABOLISM; DISEASE COURSE; ENDOCYTOSIS; ENDOPLASMIC RETICULUM; ENDOPLASMIC RETICULUM STRESS; EXCITOTOXICITY; FRONTOTEMPORAL DEMENTIA; GENE MUTATION; HUMAN; IMMUNOHISTOLOGY; IMMUNOSUPPRESSIVE TREATMENT; LIPID METABOLISM; LYSOSOME MEMBRANE; LYSOSOME STORAGE DISEASE; MITOCHONDRIAL MEMBRANE; MUCOPOLYSACCHARIDOSIS; MYELINATION; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NEURONAL CEROID LIPOFUSCINOSIS; NEUROTRANSMISSION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; SYNAPTIC MEMBRANE; THALAMOCORTICAL TRACT;

BIOCHEMICAL ABNORMALITIES; GLIAL ACTIVATION; PATHOGENESIS; SELECTIVE NEURON LOSS; STORAGE MATERIAL ACCUMULATION; SYNAPTIC PATHOLOGY;

ANIMALS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; LYSOSOMES; MEMBRANE PROTEINS; MUTATION; NEURONAL CEROID-LIPOFUSCINOSES; PHENOTYPE;

EID: 84881552764     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2013.05.014     Document Type: Review

References (169)

1. Lerner T.J., D'Arigo K.L., Haines J.L., Doggett N.A., Taschner P.E., de Vos N., Buckler A.J. Isolation of genes from the Batten candidate region using exon amplification. Batten Disease Consortium. Am. J. Med. Genet. 1995, 57:320-323.
2. Vesa J., Hellsten E., Verkruyse L.A., Camp L.A., Rapola J., Santavuori P., Hofmann S.L., Peltonen L. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature 1995, 376:584-587.
3. Sleat D.E., Donnelly R.J., Lackland H., Liu C.G., Sohar I., Pullarkat R.K., Lobel P. Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science 1997, 277:1802-1805.
4. Nosková L., Stránecký V., Hartmannová H., Přistoupilová A., Barešová V., Ivánek R., Hůlková H., Jahnová H., van der Zee J., Staropoli J.F., Sims K.B., Tyynelä J., Van Broeckhoven C., Nijssen P.C., Mole S.E., Elleder M., Kmoch M.S. Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. Am. J. Hum. Genet. 2011, 89:241-252.
5. Smith K.R., Damiano J., Franceschetti S., Carpenter S., Canafoglia L., Morbin M., Rossi G., Pareyson D., Mole S.E., Staropoli J.F., Sims K.B., Lewis J., Lin W.L., Dickson D.W., Dahl H.H., Bahlo M., Berkovic S.F. Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. Am. J. Hum. Genet. 2012, 90:1102-1107.
6. Smith K.R., Dahl H.-H.M., Canafoglia L., Andermann E., Damiano J., Morbin M., Bruni A.C., Giaccone G., Cossette P., Saftig P., Grötzinger J., Schwake M., Andermann F., Staropoli J.F., Sims K.B., Mole S.E., Franceschetti S., Alexander N.A., Cooper J.D., Chapman H.A., Carpenter S., Berkovic S.F., Bahlo M. Cathepsin F mutations cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis. Hum. Mol. Genet. 2013, 22:1417-1423.
7. Staropoli J.F., Karaa A., Lim E.T., Kirby A., Elbalalesy N., Romansky S.G., Leydiker K.B., Coppel S.H., Barone R., Xin W., MacDonald M.E., Abdenur J.E., Daly M.J., Sims K.B., Cotman S.L. A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the ubiquitin-proteasome system. Am. J. Hum. Genet. 2012, 91:202-208.
8. Bras J., Verloes A., Schneider S.A., Mole S.E., Guerreiro R.J. Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosis. Hum. Mol. Genet. 2012, 21:2646-2650.
9. Kousi M., Lehesjoki A.-E., Mole S.E. Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Hum. Mutat. 2012, 33:42-63.
10. Warrier V., Vieira M., Mole S.E. Genetic basis and phenotypic correlations of the neuronal ceroid lipofusinoses. Biochim. Biophys. Acta Mar 28 2013, (doi:pii: S0925-4439(13)00091-4. http://dx.doi.org/10.1016/j.bbadis.2013.03.017. [Epub ahead of print]).
11. Zeman W., Donahue S. Fine structure of the lipid bodies in juvenile amaurotic idiocy. Acta Neuropathol. 1963, 3:144-149.
12. Zeman W., Dyken P. Neuronal ceroid-lipofuscinosis (Batten's disease): relationship to amaurotic family idiocy?. Pediatrics 1969, 44:570-583.
13. Zeman W., Donahue S., Dyken P., Green J. The neuronal ceroid lipofuscinosis (Batten-Vogt syndrome). Handbook of clinical neurology 1970, 588-679. Elsevier/North-Holland Biomedical Press, Amsterdam. P.J. Vinken, G.W. Bruyn (Eds.).
14. Palmer D.N., Husbands D.R., Winter P.J., Blunt J.W., Jolly R.D. Ceroid lipofuscinosis in sheep. I. Bis(monoacylglycero)phosphate, dolichol, ubiquinone, phospholipids, fatty acids, and fluorescence in liver lipopigment lipids. J. Biol. Chem. 1986, 261:1766-1772.
15. Palmer D.N., Barns G., Husbands D.R., Jolly R.D. Ceroid lipofuscinosis in sheep. II. The major component of the lipopigment in liver, kidney, pancreas and brain is low molecular weight protein. J. Biol. Chem. 1986, 261:1773-1777.
16. Palmer D.N., Martinus R.D., Barns G., Reeves R.D., Jolly R.D. Ovine ceroid lipofuscinosis. I. Lipopigment composition is indicative of a lysosomal proteinosis. Am. J. Med. Genet. 1988, 5:141-158.
17. Palmer D.N., Martinus R.D., Cooper S.M., Midwinter G.G., Reid J.C., Jolly R.D. Ovine ceroid lipofuscinosis: the major lipopigment protein and the lipid binding subunit of mitochondrial ATP synthase have the same NH2 terminal sequence. J. Biol. Chem. 1989, 264:5736-5740.
18. Palmer D.N., Bayliss S.L., Clifton P.A., Grant V.J. Storage bodies in the ceroid lipofuscinoses (Batten disease): low molecular weight components, unusual amino acids and reconstitution of fluorescent bodies from non-fluorescent components. J. Inherit. Metab. Dis. 1993, 16:292-295.
19. Palmer D.N., Oswald M.J., Westlake V.J., Kay G.W. The origin of fluorescence in the neuronal ceroid lipofuscinoses (Batten disease) and neuron cultures from affected sheep for studies of neurodegeneration. Arch. Gerontol. Geriatr. 2002, 34:343-357.
20. Faust J.R., Rodman J.S., Daniel P.F., Dice J.F., Bronson R.T. Two related proteolipids and dolichol-linked oligosaccharides accumulate in motor neuron degeneration mice (mnd/mnd), a model for neuronal ceroid lipofuscinosis. J. Biol. Chem. 1994, 1269:10150-10155.
21. Herva R., Tyynel[U+04D3] J., Hirvasniemi A., Syrjakallio-Ylitalo M., Haltia M. Northern epilepsy: a novel form of neuronal ceroid-lipofuscinosis. Brain Pathol. 2000, 10:215-222.
22. Kominami E., Ezaki J., Muno D., Ishido K., Ueno T., Wolfe L.S. Specific storage of subunit c of mitochondrial ATP synthase in lysosomes of neuronal ceroid lipofuscinosis (Batten's disease). J. Biochem. 1992, 111:278-282.
23. Palmer D.N., Fearnley I.M., Walker J.E., Hall N.A., Lake B.D., Wolfe L.S., Haltia M., Martinus R.D., Jolly R.D. Mitochondrial ATP synthase subunit c storage in the ceroid-lipofuscinoses (Batten Disease). Am. J. Med. Genet. 1992, 42:561-567.
24. Palmer D.N., Jolly R.D., van Mil H.C., Tyynelä J., Westlake V.J. Different patterns of hydrophobic protein storage in different forms of neuronal ceroid-lipofuscinosis. Neuropediatrics 1997, 28:45-48.
25. Tyynelä J., Suopanki J., Santavuori P., Baumann M., Haltia M. Variant late infantile neuronal ceroid-lipofuscinosis: pathology and biochemistry. J. Neuropathol. Exp. Neurol. 1997, 56:369-375.
26. Chen R., Fearnley I.M., Palmer D.N., Walker J.E. Lysine 43 is trimethylated in subunit c from bovine mitochondrial ATP synthase and in storage bodies associated with Batten disease. J. Biol. Chem. 2004, 279:21883-21887.
27. Watt I.N., Montgomery M.G., Runswick M.J., Leslie A.G.W., Walker J.E. Bioenergetic cost of making an adenosine triphosphate molecule in animal mitochondria. Proc. Natl. Acad. Sci. U. S. A. 2010, 107(2010):16823-16827.
28. Fearnley I.M., Walker J.E., Martinus R.D., Jolly R.D., Kirkland K.B., Shaw G.J., Palmer D.N. The major protein stored in ovine ceroid lipofuscinosis is identical to the DCCD-reactive proteolipid of mitochondrial ATP synthase. Biochem. J. 1990, 268:751-775.
29. Nijssen P.C., Ceuterick C., van Diggelen O.P., Elleder M., Martin J.J., Teepen J.L., Tyynelä J., Roos R.A. Autosomal dominant adult neuronal ceroid lipofuscinosis: a novel form of NCL with granular osmiophilic deposits without palmitoyl protein thioesterase 1 deficiency. Brain Pathol. 2003, 13:574-581.
30. Tyynelä J., Palmer D.N., Baumann M., Haltia M. Storage of saposins A and D in infantile neuronal ceroid lipofuscinosis. FEBS Lett. 1993, 330:8-12.
31. Tyynelä J., Sohar I., Sleat D.E., Gin R.M., Donnelly R.J., Baumann M., Haltia M., Lobel P. A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration. EMBO J. 2000, 19:2786-2792.
32. Koike M., Nakanishi H., Saftig P., Ezaki J., Isahara K., Ohsawa Y., Schulz-Schaeffer W., Watanabe T., Waguri S., Kametaka S., Shibata M., Yamamoto K., Kominami E., Peters C., von Figura K., Uchiyama Y. Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons. J. Neurosci. 2000, 15:6898-6906.
33. Lake B.D., Hall N.A. Immunolocalization studies of subunit c in late-infantile and juvenile Batten disease. J. Inherit. Metab. Dis. 1993, 16:263-266.
34. Elleder M., Sokolová J., Hrebícek M. Follow-up study of subunit c of mitochondrial ATP synthase in Batten disease and in unrelated lysosomal disorders. Acta Neuropathol. 1997, 93:379-390.
35. Ryazantsev S., Yu W.-H., Zhao H.-Z., Neufeld N.F., Ohmi K. Lysosomal accumulation of SCMAS (subunit c of mitochondrial ATP synthase) in neurons of the mouse model of mucopolysaccharidosis IIIB. Mol. Genet. Metab. 2007, 90:393-401.
36. Bellizzi J.J., Widom J., Kemp C., Lu J.Y., Das A.K., Hofmann S.L., Clardy J. The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:4573-4578.
37. Lu J.Y., Verkruyse L.A., Hofmann S.L. Lipid thioesters derived from acylated proteins accumulate in infantile neuronal ceroid lipofuscinosis: correction of the defect in lymphoblasts by recombinant palmitoyl-protein thioesterase. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:10046-10050.
38. Hofmann S.L., Lu J.Y. Metabolic labeling of protein-derived lipid thioesters in palmitoyl protein thioesterase-deficient cells. Methods Mol. Biol. 1999, 116:213-219.
39. Hofmann S.L., Verkruyse L.A. Fatty acid analysis of protein-derived lipid thioesters isolated from palmitoyl-protein thioesterase-deficient cells. Methods Mol. Biol. 1999, 116:221-228.
40. Ezaki J., Takeda-Ezaki M., Kominami E. Tripeptidyl peptidase I, the late infantile neuronal ceroid lipofuscinosis gene product, initiates the lysosomal degradation of subunit c of ATP synthase. J. Biochem. 2000, 128:509-516.
41. Lin L., Lobel P. Production and characterization of recombinant human CLN2 protein for enzyme-replacement therapy in late infantile neuronal ceroid lipofuscinosis. Biochem. J. 2001, 357:49-55.
42. Xu S., Wang L., El-Banna M., Sohar I., Sleat D.E., Lobel P. Large-volume intrathecal enzyme delivery increases survival of a mouse model of late infantile neuronal ceroid lipofuscinosis. Mol. Ther. 2011, 19:1842-1848.
43. Tian Y., Sohar I., Taylor J.W., Lobel P. Determination of the substrate specificity of tripeptidyl-peptidase I using combinatorial peptide libraries and development of improved fluorogenic substrates. J. Biol. Chem. 2006, 281:6559-6572.
44. Metcalf P., Fusek M. Two crystal structures for cathepsin D: the lysosomal targeting signal and active site. EMBO J. 1993, 12:1293-1302.
45. Sleat D.E., Lackland H., Wang Y., Sohar I., Xiao G., Li H., Lobel P. The human brain mannose 6-phosphate glycoproteome: a complex mixture composed of multiple isoforms of many soluble lysosomal proteins. Proteomics 2005, 5:1520-1532.
46. Sleat D.E., Zheng H., Lobel P. The human urine mannose 6-phosphate glycoproteome. Biochim. Biophys. Acta 2007, 1774:368-372.
47. Sleat D.E., Della Valle M.C., Zheng H., Moore D.F., Lobel P. The mannose 6-phosphate glycoprotein proteome. J. Proteome Res. 2008, 7:3010-3021.
48. Ezaki J., Takeda-Ezaki M., Koike M., Ohsawa Y., Taka H., Mineki R., Murayama K., Uchiyama Y., Ueno T., Kominami E. Characterization of Cln3p, the gene product responsible for juvenile neuronal ceroid lipofuscinosis, as a lysosomal integral membrane glycoprotein. J. Neurochem. 2003, 87:1296-1308.
49. Fossale E., Wolf P., Espinola J.A., Lubicz-Nawrocka T., Teed A.M., Gao H., Dorotea Rigamonti D., Cattaneo E., MacDonald M.E., Cotman S.L. Membrane trafficking and mitochondrial abnormalities precede subunit c deposition in a cerebellar cell model of juvenile neuronal ceroid lipofuscinosis. BMC Neurosci. 2004, 5:57.
50. Kyttälä A., Ihrke G., Vesa J., Schell M.J., Luzio J.P. Two motifs target Batten disease protein CLN3 to lysosomes in transfected nonneuronal and neuronal cells. Mol. Biol. Cell 2004, 15:1313-1323.
51. Siintola E., Topcu M., Aula N., Lohi H., Minassian B.A., Paterson A.D., Liu X.Q., Wilson C., Lahtinen U., Anttonen A.K., Lehesjoki A.-E. The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter. Am. J. Hum. Genet. 2007, 81:136-146.
52. Lonka L., Salonen T., Siintola E., Kopra O., Lehesjoki A.-E., Jalanko A. Localization of wild-type and mutant neuronal ceroid lipofuscinosis CLN8 proteins in non-neuronal and neuronal cells. J. Neurosci. Res. 2004, 76:862-871.
53. Gao H., Boustany R.-M., Espinola J.A. Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse. Am. J. Hum. Genet. 2002, 70:324-335.
54. Heine C., Koch B., Storch S., Kohlschütter A., Palmer D.N., Braulke T. Defective endoplasmic reticulum-resident membrane protein CLN6 affects lysosomal degradation of endocytosed arylsulfatase A. J. Biol. Chem. 2004, 279:22347-22352.
55. Mole S.E., Michaux G., Codlin S., Wheeler R.B., Sharp J.D., Cutler D.F. CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein. Exp. Cell Res. 2004, 298:399-406.
56. Zhong N.A., Moroziewicz D.N., Ju W., Wisniewski K.E., Jurkiewicz A., Brown W.T. CLN-encoded proteins do not interact with each other. Neurogenet. 2000, 3:41-44.
57. Vesa J., Chin M.H., Oelgeschläger K., Isosomppi J., Dell Angelica E.C., Jalanko A., Peltonen L. Ceroid lipofuscinoses are connected at the molecular level: Interaction of CLN5 protein with CLN2 and CLN3. Mol. Biol. Cell 2002, 13:2410-2420.
58. Lyly A., von Schantz C., Heine C., Schmiedt M.L., Sipila T., Jalanko A., Kyttälä A. Novel interactions of CLN5 support molecular networking between neuronal ceroid lipofuscinosis proteins. BMC Cell Biol. 2009, 10:83.
59. Isosomppi J., Vesa J., Jalanko A., Peltonen L. Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein. Hum. Mol. Genet. 2002, 11:885-891.
60. Schmiedt M.L., Bessa C., Heine C., Ribeiro M.G., Jalanko A., Kyttälä A. The neuronal ceroid lipofuscinosis protein CLN5: new insights into cellular maturation, transport, and consequences of mutations. Hum. Mutat. 2010, 31:356-365.
61. Lebrun A.H., Storch S., Ruschendorf F., Schmiedt M.L., Kyttälä A., Mole S.E., Kitzmüller C., Saar K., Mewasingh L.D., Boda V., Kohlschütter A., Ullrich K., Braulke T., Schulz A. Retention of lysosomal protein CLN5 in the endoplasmic reticulum causes neuronal ceroid lipofuscinosis in an Asian sibship. Hum. Mutat. 2009, 30:E651-E661.
62. Walkley S.U., March P.A., Schroeder C.E., Wurzelmann S., Jolly R.D. Pathogenesis of brain dysfunction in Batten disease. Am. J. Med. Genet. 1995, 57:196-203.
63. March P.A., Wurzelmann S., Walkley S.U. Morphological alterations in neocortical and cerebellar GABAergic neurons in canine Batten's disease. Am. J. Med. Genet. 1995, 57:204-212.
64. Cooper J.D. Moving towards therapies for juvenile Batten disease?. Exp. Neurol. 2008, 211:329-331.
65. Bible E., Gupta P., Hofmann S.L., Cooper J.D. Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis. Neurobiol. Dis. 2004, 16:346-359.
66. Cooper J.D., Messer A., Feng A.K., Chua-Couzens J., Mobley W.C. Apparent loss and hypertrophy of interneurons in a mouse model of neuronal ceroid lipofuscinosis: evidence for partial response to insulin-like growth factor-1 treatment. J. Neurosci. 1999, 19:2556-2567.
67. Kielar C., Maddox L., Bible E., Pontikis C.C., Macauley S.L., Griffey M.A., Wong M., Sands M.S., Cooper J.D. Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis. Neurobiol. Dis. 2007, 25:150-162.
68. Oswald M.J., Kay G.W., Palmer D.N. Changes in GABAergic neuron distribution in situ and in neuron cultures in ovine (OCL6) Batten disease. Eur. J. Paediatr. Neurol. 2001, 5:135-142.
69. -/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation. Brain Res. 2004, 1023:231-242.
70. 1H NMR-based metabolomics indicates a neurotransmitter cycling deficit in cerebral tissue from a mouse model of Batten disease. J. Biol. Chem. 2005, 280:42508-42514.
71. Pears M.R., Salek R.M., Palmer D.N., Kay G.W., Mortishire-Smith R.J., Griffin J.L. Metabolomic investigation of CLN6 neuronal ceroid lipofuscinosis in affected South Hampshire sheep. J. Neurosci. Res. 2007, 85:3494-3504.
72. Kay G.W., Verbeek M.M., Furlong J.M., Willemsen M.A., Palmer D.N. Neuropeptide changes and neuroactive amino acids in CSF from humans and sheep with neuronal ceroid lipofuscinoses (NCLs, Batten disease). Neurochem. Int. 2009, 55:783-788.
73. Jolly R.D., Palmer D.N., Studdert V.P., Sutton R., Kelly W., Koppang N., Dahme G., Hartley W.J., Patterson J., Riis R. Canine ceroid-lipofuscinoses: a review and classification. J. Small Anim. Pract. 1994, 35:299-306.
74. Palmer D.N., Tammen I., Drögemüller C., Johnson G.S., Katz M.L., Lingaas F. Large animal models. The neuronal ceroid lipofuscinoses (Batten disease) 2011, 284-320. Oxford University Press Inc., New York. 2nd edition. S.E. Mole, R.E. Williams, H.H. Goebel (Eds.).
75. Cooper J.D. Progress towards understanding the neurobiology of Batten disease or neuronal ceroid lipofuscinosis. Curr. Opin. Neurol. 2003, 16:121-128.
76. Cooper J.D., Russell C., Mitchison H.M. Progress towards understanding disease mechanisms in small vertebrate models of neuronal ceroid lipofuscinosis. Biochim. Biophys. Acta 2006, 1762:873-889.
77. Chang M., Cooper J.D., Sleat D.E., Cheng S.H., Dodge J.C., Passini M.A., Lobel P., Davidson B.L. Intraventricular enzyme replacement improves disease phenotypes in a mouse model of late infantile neuronal ceroid lipofuscinosis. Mol. Ther. 2008, 16:649-656.
78. Cooper J.D. The neuronal ceroid lipofuscinoses: the same, but different?. Biochem. Soc. Trans. 2010, 38:1448-1452.
79. Jolly R.D., Shimada A., Dopfmer I., Slack P.M., Birtles M.J., Palmer D.N. Ceroid-lipofuscinosis (Batten's disease): pathogenesis and sequential neuropathological changes in the ovine model. Neuropathol. Appl. Neurobiol. 1989, 15:371-383.
80. Mayhew I.G., Jolly R.D., Pickett B.T., Slack P.M. Ceroid-lipofuscinosis (Batten's disease): pathogenesis of blindness in the ovine model. Neuropathol. Appl. Neurobiol. 1985, 11:273-290.
81. Oswald M.J., Palmer D.N., Kay G.W., Shemilt S.J., Rezaie P., Cooper J.D. Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6). Neurobiol. Dis. 2005, 20:49-63.
82. Oswald M.J., Palmer D.N., Kay G.W., Barwell K.J., Cooper J.D. Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis. Neurobiol. Dis. 2008, 32:50-65.
83. Haltia M. The neuronal ceroid-lipofuscinoses. J. Neuropathol. Exp. Neurol. 2003, 62:1-13.
84. Sleat D.E., Wiseman J.A., El-Banna M., Kim K.H., Mao Q., Price S., Macauley S.L., Sidman R.L., Shen M.M., Zhao Q., Passini M.A., Davidson B.L., Stewart G.R., Lobel P. A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on targeted disruption of the CLN2 gene results in a loss of tripeptidyl-peptidase I activity and progressive neurodegeneration. J. Neurosci. 2004, 24:9117-9126.
85. Kay G.W., Jay N.P., Palmer D.N. The specific loss of GnRH-positive neurons from the hypothalamus of sheep with CLN6 neuronal ceroid lipofuscinosis occurs without glial activation and has only minor effects on reproduction. Neurobiol. Dis. 2011, 41:614-623.
86. Griffey M.A., Wozniak D., Wong M., Bible E., Johnson K., Rothman S.M., Wentz A.E., Cooper J.D., Sands M.S. CNS-directed AAV2-mediated gene therapy ameliorates functional deficits in a murine model of infantile neuronal ceroid lipofuscinosis. Mol. Ther. 2006, 13:538-547.
87. Kay G.W., Palmer D.N., Rezaie P., Cooper J.D. Activation of non-neuronal cells within the prenatal developing brain of sheep with neuronal ceroid lipofuscinosis. Brain Pathol. 2006, 16:110-116.
88. Kuronen M., Hermansson M., Manninen O., Zech I., Talvitie M., Laitinen T., Gröhn O., Somerharju P., Eckhardt M., Cooper J.D., Lehesjoki A.-E., Lahtinen U., Kopra O. Galactolipid deficiency in the early pathogenesis of neuronal ceroid lipofuscinosis model Cln8mnd: implications to delayed myelination and oligodendrocyte maturation. Neuropathol. Appl. Neurobiol. 2012, 38:471-486.
89. Macauley S.L., Pekny M., Sands M.S. The role of attenuated astrocyte activation in infantile neuronal ceroid lipofuscinosis. J. Neurosci. 2011, 31:15575-15585.
90. Partanen S., Haapanen A., Kielar C., Pontikis C., Alexander N.A., Inkinen T., Saftig P., Gillingwater T.H., Cooper J.D., Tyynelä J. Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis. J. Neuropathol. Exp. Neurol. 2008, 67:16-29.
91. δex7/8 knock-in mouse model of Batten disease. Neurobiol. Dis. 2005, 20:823-836.
92. Schmiedt M.L., Blom T., Blom T., Kopra O., Wong A., von Schantz-Fant C., Ikonen E., Kuronen M., Jauhiainen M., Cooper J.D., Jalanko A. Cln5-deficiency in mice leads to microglial activation, defective myelination and changes in lipid metabolism. Neurobiol. Dis. 2012, 46:19-29.
93. von Schantz C., Kielar C., Hansen S.N., Pontikis C.C., Alexander N.A., Kopra O., Jalanko A., Cooper J.D. Progressive thalamocortical neuron loss in Cln5 deficient mice: distinct effects in Finnish variant late infantile NCL. Neurobiol. Dis. 2009, 34:308-319.
94. Weimer J.M., Custer A.W., Benedict J.W., Alexander N.A., Kingsley E., Federoff H.J., Cooper J.D., Pearce D.A. Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons. Neurobiol. Dis. 2006, 22:284-293.
95. Mitchison H.M., Bernard D.J., Greene N.D., Cooper J.D., Junaid M.A., Pullarkat R.K., de Vos N., Breuning M.H., Owens J.W., Mobley W.C., Gardiner R.M., Lake B.D., Taschner P.E., Nussbaum R.L. Targeted disruption of the Cln3 gene provides a mouse model for Batten disease. The Batten Mouse Model Consortium. Neurobiol. Dis. 1999, 6:321-334.
96. Tyynelä J., Cooper J.D., Khan M.N., Shemilt S.J., Haltia M. Hippocampal pathology in the human neuronal ceroid-lipofuscinoses: distinct patterns of storage deposition, neurodegeneration and glial activation. Brain Pathol. 2004, 14:349-357.
97. Wu Y.P., Proia R.L. Deletion of macrophage-inflammatory protein 1 alpha retards neurodegeneration in Sandhoff disease mice. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:8425-8430.
98. Tammen I., Houweling P.J., Frugier T., Mitchell N.L., Kay G.W., Cavanagh J.A., Cook R.W., Raadsma H.W., Palmer D.N. A missense mutation (c.184C>T) in ovine CLN6 causes neuronal ceroid lipofuscinosis in Merino sheep whereas affected South Hampshire sheep have reduced levels of CLN6 mRNA. Biochim. Biophys. Acta 2006, 1762:898-905.
99. Bhat R., Steinman L. Innate and adaptive autoimmunity directed to the central nervous system. Neuron 2009, 64:123-132.
100. Block M.L., Hong J.S. Chronic microglial activation and progressive dopaminergic neurotoxicity. Biochem. Soc. Trans. 2007, 35:1127-1132.
101. Beal M.F. Experimental models of Parkinson's disease. Nat. Rev. Neurosci. 2001, 2:325-334.
102. Hirsch E.C., Hunot S. Neuroinflammation in Parkinson's disease: a target for neuroprotection?. Lancet Neurol. 2009, 8:382-397.
103. Vila N., Chamorro A., Castillo J., Dávalos A. Glutamate, interleukin-6, and early clinical worsening in patients with acute stroke. Stroke 2001, 32:1234-1237.
104. Jeyakumar M., Thomas R., Elliot-Smith E., Smith D.A., van der Spoel A.C., d'Azzo A., Perry V.H., Butters T.D., Dwek R.A., Platt F.M. Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain 2003, 126:974-987.
105. Zhang Z., Lee Y.C., Kim S.J., Choi M.S., Tsai P.C., Saha A., Wei H., Xu Y., Xiao Y.J., Zhang P., Heffer A., Mukherjee A.B. Production of lysophosphatidylcholine by cPLA2 in the brain of mice lacking PPT1 is a signal for phagocyte infiltration. Hum. Mol. Genet. 2007, 16:837-847.
106. Saha A., Kim S.J., Zhang Z., Lee Y.C., Sarkar C., Tsai P.C., Mukherjee A.B. RAGE signaling contributes to neuroinflammation in infantile neuronal ceroid lipofuscinosis. FEBS Lett. 2008, 582:3823-3831.
107. Barry L.A., Palmer D.N., Mitchell N.L., Kay G.W., Jay N.P. Increased expression of TNF-α, IL-1β, TGF-β and IL-10 in the brains of sheep with CLN6 NCL. 13th International Conference on Neuronal Ceroid Lipofuscinoses, London, UK 2012.
108. Das S., Basu A. Inflammation: a new candidate in modulating adult neurogenesis. J. Neurosci. Res. 2008, 86:1199-1208.
109. Lim M.J., Alexander N., Benedict J.W., Chattopadhyay S., Shemilt S.J., Guérin C.J., Cooper J.D., Pearce D.A. IgG entry and deposition are components of the neuroimmune response in Batten disease. Neurobiol. Dis. 2007, 25:239-251.
110. Saha A., Sarkar C., Singh S.P., Zhang Z., Munasinghe J., Peng S., Chandra G., Kong E., Mukherjee A.B. The blood-brain barrier is disrupted in a mouse model of infantile neuronal ceroid lipofuscinosis: amelioration by resveratrol. Hum. Mol. Genet. 2012, 21:2233-2244.
111. Seehafer S.S., Ramirez-Montealegre D., Wong A.M., Chan C.H., Castaneda J., Horak M., Ahmadi S.M., Lim M.J., Cooper J.D., Pearce D.A. Immunosuppression alters disease severity in juvenile Batten disease mice. J. Neuroimmunol. 2011, 230:169-172.
112. Aberg L., Talling M., Härkönen T., Lönnqvist T., Knip M., Alen R., Rantala H., Tyynelä J. Intermittent prednisolone and autoantibodies to GAD65 in juvenile neuronal ceroid lipofuscinosis. Neurology 2008, 70:1218-1220.
113. Groh J., Kühl T.G., Ip C.W., Nelvagal H.R., Sri S., Duckett S., Mirza M., Langmann T., Cooper J.D., Martini R. Immune cells perturb axons and impair neuronal survival in a mouse model of infantile neuronal ceroid lipofuscinosis. Brain 2013, 136:1083-1101.
114. Bourre J.M., Haltia M., Daudu O., Monge M., Baumann N. Infantile form of so called neuronal ceroid lipofuscinosis: Lipid biochemical studies, fatty acid analysis of cerebroside sulfatides and shingomyelin, myelin density profile and lipid composition. Eur. Neurol. 1979, 18:312-321.
115. Hagberg B., Sourander P., Svennerholm L. Late infantile progressive encephalopathy with disturbed polyunsaturated fat metabolism. Acta Paediatr. Scand. 1968, 5:495-499.
116. Nevalainen T.J., Panelius M., Riekkinen P.J. Neuronal ceroid lipofuscinosis. Report of two cases with neurochemical and morphological observations. Eur. Neurol. 1973, 9:298-314.
117. Van Dessel G., Lagrou A., Martin J.J., Dierick W., A. case of infantile generalized ceroid-lipofuscinosis. Neurochemical observations [proceedings]. Arch. Int. Physiol. Biochim. 1977, 85:1023-1025.
118. Svennerholm L., Hagberg B., Haltia M., Sourander P., Vanier M.-T. Polyunsaturated fatty acid lipidosis. II. Lipid biochemical studies. Acta Paediatr. Scand. 1975, 64:489-496.
119. Svennerholm L., Fredman P., Jungbjer B., Månsson J.E., Rynmark B.M., Boström K., Hagberg B., Norén L., Santavuori P. Large alterations in ganglioside and neutral glycosphingolipid patterns in brains from cases with infantile neuronal ceroid lipofuscinosis/polyunsaturated fatty acid lipidosis. J. Neurochem. 1987, 49:1772-1783.
120. Palmer D.N., Husbands D.R., Jolly R.D. Phospholipid fatty acids in brains of normal sheep and sheep with ceroid lipofuscinosis. Biochim. Biophys. Acta 1985, 834:159-163.
121. Käkelä R., Somerharju P., Tyynelä J. Analysis of phospholipid molecular species in brains from patients with infantile and juvenile neuronal-ceroid lipofuscinosis using liquid chromatography-electrospray ionization mass spectrometry. J. Neurochem. 2003, 84:1051-1065.
122. Hermansson M., Käkelä R., Berghäll M., Lehesjoki A.-E., Somerharju P., Lahtine U. Mass spectrometric analysis reveals changes in phospholipid, neutral sphingolipid and sulfatide molecular species in progressive epilepsy with mental retardation, EPMR, brain: a case study. J. Neurochem. 2005, 95:609-617.
123. Zhang C.K., Stein P.B., Liu J., Wang Z., Yang R., Cho J.H., Gregersen P.K., Aerts J.M., Zhao H., Pastores G.M., Mistry P.K. Genome-wide association study of N370S homozygous Gaucher disease reveals the candidacy of CLN8 gene as a genetic modifier contributing to extreme phenotypic variation. Am. J. Hematol. 2012, 87:377-383.
124. Ahtiainen L., Kolikova J., Mutka A.L., Luiro K., Gentile M., Ikonen E., Khiroug L., Jalanko A., Kopra O. Palmitoyl protein thioesterase 1 (Ppt1)-deficient mouse neurons show alterations in cholesterol metabolism and calcium homeostasis prior to synaptic dysfunction. Neurobiol. Dis. 2007, 28:52-64.
125. Lyly A., Marjavaara S.K., Kyttälä A., Uusi-Rauva K., Luiro K., Kopra O., Martinez L.O., Tanhuanpää K., Kalkkinen N., Suomalainen A., Jauhiainen M., Jalanko A. Deficiency of the INCL protein Ppt1 results in changes in ectopic F1-ATP synthase and altered cholesterol metabolism. Hum. Mol. Genet. 2008, 17:1406-1417.
126. Jabs S., Quitsch A., Käkelä R., Koch B., Tyynelä J., Brade H., Glatzel M., Walkley S., Saftig P., Vanier M.-T., Braulke T. Accumulation of bis(monoacylglycero)phosphate and gangliosides in mouse models of neuronal ceroid lipofuscinosis. J. Neurochem. 2008, 106:1415-1425.
127. Teixeira C.A., Lin S., Mangas M., Quinta R., Bessa C.J., Ferreira C., Sá Miranda M.C., Boustany R.-M., Ribeiro M.G. Gene expression profiling in vLINCL CLN6-deficient fibroblasts: insights into pathobiology. Biochim. Biophys. Acta 2006, 1762:637-646.
128. Mutka A.-L., Haapanen A., Käkelä R., Lindfors M., Wright A.K., Inkinen T., Hermansson M., Rokka A., Corthals G., Jauhiainen M., Gillingwater T.H., Ikonen E., Tyynelä J. Murine cathepsin D deficiency is associated with dysmyelination/myelin disruption and accumulation of cholesteryl esters in the brain. J. Neurochem. 2010, 112:193-203.
129. Mitchison H.M., Lim M.J., Cooper J.D. Selectivity and types of cell death in the neuronal ceroid lipofuscinoses. Brain Pathol. 2004, 14:86-96.
130. Koike M., Shibata M., Waguri S., Yoshimura K., Tanida I., Kominami E., Gotow T., Peters C., von Figura K., Mizushima N., Saftig P., Uchiyama Y. Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease). Am. J. Pathol. 2005, 167:1713-1728.
131. Cao Y., Espinola J.A., Fossale E., Massey A.C., Cuervo A.M., MacDonald M.E., Cotman S.L. Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis. J. Biol. Chem. 2006, 281:20483-20493.
132. Cao Y., Staropoli J.F., Biswas S., Espinola J.A., MacDonald M.E., Lee J.M., Cotman S.L. Distinct early molecular responses to mutations causing vLINCL and JNCL presage ATP synthase subunit c accumulation in cerebellar cells. PLoS One 2011, 6. (e17118-1-e17118-14).
133. Thelen M., Damme M., Schweizer M., Hagel C., Wong A.M., Cooper J.D., Braulke T., Galliciotti G. Disruption of the autophagy-lysosome pathway is involved in neuropathology of the nclf mouse model of neuronal ceroid lipofuscinosis. PLoS One 2012, 7:e35493.
134. Luiro K., Yliannala K., Ahtiainen L., Maunu H., Järvelä I., Kyttälä A., Jalanko A. Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to defects in the endocytic pathway. Hum. Mol. Genet. 2004, 13:3017-3027.
135. Luiro K., Kopra O., Lehtovirta M., Jalanko A. CLN3 protein is targeted to neuronal synapses but excluded from synaptic vesicles: new clues to Batten disease. Hum. Mol. Genet. 2001, 10:2123-2131.
136. Persaud-Sawin D.A., McNamara J.O., Vandongen R.S., Boustany R.-M. A galactosylceramide binding domain is involved in trafficking of CLN3 from Golgi to rafts via recycling endosomes. Pediatr Res. 2004, 56:449-463.
137. Codlin S., Haines R.L., Mole S.E. Btn1 affects endocytosis, polarization of sterol-rich membrane domains and polarized growth in Schizosaccharomyces pombe. Traffic 2008, 9:936-950.
138. Kama R., Kanneganti V., Ungermann C., Gerst J.E. The yeast Batten disease orthologue Btn1 controls endosome-Golgi retrograde transport via SNARE assembly. J. Cell Biol. 2011, 195:203-215.
139. Uusi-Rauva K., Kyttälä A., van der Kant R., Vesa J., Tanhuanpää K., Neefjes J., Olkkonen V.M., Jalanko A. Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins and modifies location of late endosomal compartments. Cell. Mol. Life Sci. 2012, 69:2075-2089.
140. Mamo A., Jules F., Dumaresq-Doiron K., Costantino S., Lefrancois S. The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal sorting. Mol. Cell. Biol. 2012, 32:1855-1866.
141. Ahtiainen L., Luiro K., Kauppi M., Tyynelä J., Kopra O., Jalanko A. Palmitoyl protein thioesterase 1 (PPT1) deficiency causes endocytic defects connected to abnormal saposin processing. Exp. Cell Res. 2006, 312:1540-1553.
142. Buff H., Smith A.C., Korey C.A. Genetic modifiers of Drosophila palmitoyl-protein thioesterase 1-induced degeneration. Genetics 2007, 176:209-220.
143. Saja S., Buff H., Smith A.C., Williams T.S., Korey C.A. Identifying cellular pathways modulated by drosophila palmitoyl-protein thioesterase 1 function. Neurobiol. Dis. 2010, 40:135-145.
144. Virmani T., Gupta P., Liu X., Kavalali E.T., Hofmann S.L. Progressively reduced synaptic vesicle pool size in cultured neurons derived from neuronal ceroid lipofuscinosis-1 knockout mice. Neurobiol. Dis. 2005, 20:314-323.
145. Kim S.J., Zhang Z., Sarkar C., Tsai P.C., Lee Y.C., Dye L., Mukherjee A.B. Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice. J. Clin. Invest. 2008, 118:3075-3086.
146. Kielar C., Wishart T.M., Palmer A., Dihanich S., Wong A.M., Macauley S.L., Chan C.H., Sands M.S., Pearce D.A., Cooper J.D., Gillingwater T.H. Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Hum. Mol. Genet. 2009, 18:4066-4080.
147. Koch S., Molchanova S.M., Wright A.K., Edwards A., Cooper J.D., Taira T., Gillingwater T.H., Tyynelä J. Morphologic and functional correlates of synaptic pathology in the cathepsin D knockout mouse model of congenital neuronal ceroid lipofuscinosis. J. Neuropathol. Exp. Neurol. 2011, 70:1089-1096.
148. Qiao L., Hamamichi S., Caldwell K.A., Caldwell G.A., Yacoubian T.A., Wilson S., Xie Z.L., Speake L.D., Parks R., Crabtree D., Liang Q., Crimmins S., Schneider L., Uchiyama Y., Iwatsubo T., Zhou Y., Peng L., Lu Y., Standaert D.G., Walls K.C., Shacka J.J., Roth K.A., Zhang J. Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity. Mol. Brain 2008, 1:17.
149. Cullen V., Lindfors M., Ng J., Paetau A., Swinton E., Kolodziej P., Boston H., Saftig P., Woulfe J., Feany M.B., Myllykangas L., Schlossmacher M.G., Tyynelä J. Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo. Mol. Brain 2009, 2:5.
150. Sharma M., Burré J., Bronk P., Zhang Y., Xu W., Südhof T.C. CSPα knockout causes neurodegeneration by impairing SNAP-25 function. EMBO J. 2011, 31:829-841.
151. Yap C.C., Winckler B. Harnessing the power of the endosome to regulate neural development. Neuron 2012, 74:440-451.
152. Kim K.H., Sleat D.E., Bernard O., Lobel P. Genetic modulation of apoptotic pathways fails to alter disease course in tripeptidyl-peptidase 1 deficient mice. Neurosci. Lett. 2009, 453:27-30.
153. Tardy C., Sabourdy F., Garcia V., Jalanko A., Therville N., Levade T., Andrieu-Abadie N. Palmitoyl protein thioesterase 1 modulates tumor necrosis factor alpha-induced apoptosis. Biochim. Biophys. Acta 2009, 1793:1250-1258.
154. Autefage A.H., Albinet V., Garcia V., Berges H., Nicolau M.L., Therville N., Altié M.F., Caillaud C., Levade T., Andrieu-Abadie N.J. Lysosomal serine protease CLN2 regulates tumor necrosis factor-alpha-mediated apoptosis in a Bid-dependent manner. J. Biol. Chem. 2009, 284:11507-11516.
155. Tardy C., Tyynelä J., Hasilik A., Levade T., Andrieu-Abadi N. Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D. Cell Death Differ. 2003, 10:1090-1100.
156. Shacka J.J., Klocke B.J., Young C., Shibata M., Olney J.W., Uchiyama Y., Saftig P., Roth K.A. Cathepsin D deficiency induces persistent neurodegeneration in the absence of Bax-dependent apoptosis. J. Neurosci. 2007, 27:2081-2090.
157. Walls K.C., Klocke B.J., Saftig P., Shibata M., Uchiyama Y., Roth K.A., Shacka J.J. Altered regulation of phosphatidylinositol 3-kinase signaling in cathepsin D-deficient brain. Autophagy 2007, 3:222-229.
158. (δex7/8/δex7/8) cerebellar cells and reduces neuronal vulnerability to cell death via IMPase inhibition. J. Neurochem. 2011, 116:659-668.
159. δex7/8) knock-in mice, an animal model of juvenile neuronal ceroid lipofuscinosis. J. Neurosci. Res. 2008, 86:1857-1870.
160. Guarneri R., Russo D., Cascio C., D'Agostino S., Galizzi G., Bigini P., Mennini T., Guarneri P. Retinal oxidation, apoptosis and age- and sex-differences in the mnd mutant mouse, a model of neuronal ceroid lipofuscinosis. Brain Res. 2004, 1014:209-220.
161. Kim S.J., Zhang Z., Saha A., Sarkar C., Zhao Z., Xu Y., Mukherjee A.B. Omega-3 and omega-6 fatty acids suppress ER- and oxidative stress in cultured neurons and neuronal progenitor cells from mice lacking PPT1. Neurosci. Lett. 2010, 479:292-296.
162. Zhang Z., Lee Y.C., Kim S.J., Choi M.S., Tsai P.C., Xu Y., Xiao Y.J., Zhang P., Heffer A., Mukherjee A.B. Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL. Hum. Mol. Genet. 2006, 15:337-346.
163. Galizzi G., Russo D., Deidda I., Cascio C., Passantino R., Guarneri R., Bigini P., Mennini T., Drago G., Guarneri P. Different early ER-stress responses in the CLN8(mnd) mouse model of neuronal ceroid lipofuscinosis. Neurosci. Lett. 2011, 488:258-262.
164. Ugolino J., Fang S., Kubisch C., Monteiro M.J. Mutant Atp13a2 proteins involved in parkinsonism are degraded by ER-associated degradation and sensitize cells to ER-stress induced cell death. Hum. Mol. Genet. 2011, 20:3565-3577.
165. Kovács A.D., Weimer J.M., Pearce D.A. Selectively increased sensitivity of cerebellar granule cells to AMPA receptor-mediated excitotoxicity in a mouse model of Batten disease. Neurobiol. Dis. 2006, 22:575-585.
166. Kovács A.D., Pearce D.A. Attenuation of AMPA receptor activity improves motor skills in a mouse model of juvenile Batten disease. Exp. Neurol. 2008, 209:288-291.
167. Kovács A.D., Sajed A., Wong A., Szénásie G., Kiricsie P., Szabóe É., Cooper J.D., Pearce D.A. Temporary inhibition of AMPA receptors induces a prolonged improvement of motor performance in a mouse model of juvenile Batten disease. Neuropharmacology. 2011, 60:405-409.
168. Kovács A.D., Saje A., Wong A., Ramji S., Cooper J.D., Pearce D.A. Age-dependent therapeutic effect of memantine in a mouse model of juvenile Batten disease. Neuropharmacology. 2012, 63:769-775.
169. -/- mouse, a murine model of infantile neuronal ceroid lipofuscinosis. J. Neurosci. Res. 2012, 90:367-375.