A GCase Chaperone Improves Motor Function in a Mouse Model of Synucleinopathy

Neurotherapeutics

Volumn 11, Issue 4, 2014, Pages 840-856

  Richter, Franziska ^a   Fleming, Sheila M ^a   Watson, Melanie ^a   Lemesre, Vincent ^a   Pellegrino, Lee ^b   Ranes, Brian ^b   Zhu, Chunni ^a   Mortazavi, Farzad ^a   Mulligan, Caitlin K ^a   Sioshansi, Pedrom C ^a   Hean, Sindalana ^a   De La Rosa, Krystal ^a   Khanna, Richie ^b   Flanagan, John ^b   Lockhart, David J ^b   Wustman, Brandon A ^c   Clark, Sean W ^b   Chesselet, Marie Françoise ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Amicus Therapeutics   (United States)

^c Amicus Therapeutics   (United States)

Author keywords

Acid glucosidase; Alpha synuclein; Chaperone; Motor behavior; Mouse model; Parkinson s disease

Indexed keywords

AFEGOSTAT; ALPHA SYNUCLEIN; BETA GLUCOSIDASE; IMINOSUGAR; ISOFAGOMINE; PROTEIN AGGREGATE; SNCA PROTEIN, HUMAN; TARTARIC ACID DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BEHAVIOR; BRAIN; CONTROLLED STUDY; DEGENERATIVE DISEASE; DOPAMINERGIC NERVE CELL; ENZYME ACTIVITY; ENZYME STABILITY; IMMUNOREACTIVITY; INFLAMMATION; LOCOMOTION; MALE; MICROGLIA; MOTOR PERFORMANCE; MOUSE; NONHUMAN; OLFACTORY SYSTEM; PARKINSON DISEASE; SUBSTANTIA NIGRA; SYNUCLEINOPATHY; ANIMAL; ANTAGONISTS AND INHIBITORS; DISEASE MODEL; DRUG EFFECTS; ENZYMOLOGY; HUMAN; METABOLISM; MOTOR ACTIVITY; PROTEIN TRANSPORT;

ALPHA-SYNUCLEIN; ANIMALS; BETA-GLUCOSIDASE; BRAIN; DISEASE MODELS, ANIMAL; DOPAMINERGIC NEURONS; HUMANS; IMINO PYRANOSES; MALE; MICE; MOTOR ACTIVITY; PARKINSON DISEASE; PROTEIN AGGREGATES; PROTEIN TRANSPORT; SUBSTANTIA NIGRA; TARTRATES;

EID: 84919876441     PISSN: 19337213     EISSN: 18787479     Source Type: Journal    
DOI: 10.1007/s13311-014-0294-x     Document Type: Article

References (44)

1. Hardy J. Genetic analysis of pathways to Parkinson disease. Neuron 2010;68:201-216.
2. Pankratz N, Nichols WC, Elsaesser VE, P et al. Alpha-synuclein and familial Parkinson's disease. Mov Disord 2009;24:1125–1131.
3. Trojanowski JQ, Lee VM. Parkinson's disease and related alpha-synucleinopathies are brain amyloidoses. Ann N Y Acad Sci 2003;991:107–110.
4. Bultron G, Kacena K, Pearson D, et al. The risk of Parkinson's disease in type 1 Gaucher disease. J Inherit Metab Dis 2010;33:167–173.
5. Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med 2009;361:1651–1661.
6. Cookson MR. A feedforward loop links Gaucher and Parkinson's diseases? Cell 2011;146:9–11.
7. Dawson TM, Dawson VL. A lysosomal lair for a pathogenic protein pair. Sci Transl Med 2011;3:91ps28.
8. Mazzulli JR, Xu YH, Sun Y, et al. Gaucher Disease Glucocerebrosidase and alpha-Synuclein Form a Bidirectional Pathogenic Loop in Synucleinopathies. Cell 2011;146:37–52.
9. Yap TL, Velayati A, Sidransky E, Lee JC. Membrane-bound alpha-synuclein interacts with glucocerebrosidase and inhibits enzyme activity. Mol Genet Metab 2013;108:56–64.
10. Yap TL, Gruschus JM, Velayati A, et al. Alpha-synuclein interacts with Glucocerebrosidase providing a molecular link between Parkinson and Gaucher diseases. J Biol Chem 2012;286:28080–28088.
11. Gegg ME, Burke D, Heales SJ, et al. Glucocerebrosidase deficiency in substantia nigra of parkinson disease brains. Ann Neurol 2012;72:455–463.
12. Cullen V, Sardi SP, Ng J, et al. Acid beta-glucosidase mutants linked to Gaucher disease, Parkinson disease, and Lewy body dementia alter alpha-synuclein processing. Ann Neurol 2011;69:940–953.
13. Sardi SP, Clarke J, Kinnecom C, et al. CNS expression of glucocerebrosidase corrects alpha-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy. Proc Natl Acad Sci U S A 2011;108:12101–12106.
14. Schapira AH, Gegg ME. Glucocerebrosidase in the pathogenesis and treatment of Parkinson disease. Proc Natl Acad Sci U S A 2013;110:3214–3215.
15. Valenzano KJ, Khanna R, Powe AC, et al. Identification and characterization of pharmacological chaperones to correct enzyme deficiencies in lysosomal storage disorders. Assay Drug Develop Technol 2011;9:213–235.
16. Khanna R, Benjamin ER, Pellegrino L, et al. The pharmacological chaperone isofagomine increases the activity of the Gaucher disease L444P mutant form of beta-glucosidase. FEBS J 2010;277:1618–1638.
17. Steet RA, Chung S, Wustman B, Powe A, Do H, Kornfeld SA. The iminosugar isofagomine increases the activity of N370S mutant acid beta-glucosidase in Gaucher fibroblasts by several mechanisms. Proc Natl Acad Sci U S A 2006;103:13813–13818.
18. Ron I, Horowitz M. ER retention and degradation as the molecular basis underlying Gaucher disease heterogeneity. Hum Mol Genet 2005;14:2387–2398.
19. Sawkar AR, Schmitz M, Zimmer KP, et al. Chemical chaperones and permissive temperatures alter localization of Gaucher disease associated glucocerebrosidase variants. ACS Chem Biol 2006;1:235–251.
20. Fleming SM, Salcedo J, Fernagut PO, et al. Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein. J Neurosci 2004;24:9434–9440.
21. Rockenstein E, Mallory M, Hashimoto M, et al. Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters. J Neurosci Res 2002;68:568–578.
22. Lam HA, Wu N, Cely I, et al. Elevated tonic extracellular dopamine concentration and altered dopamine modulation of synaptic activity precede dopamine loss in the striatum of mice overexpressing human alpha-synuclein. J Neurosci Res 2011;89:1091–1102.
23. Chesselet MF, Richter F. Modelling of Parkinson's disease in mice. Lancet Neurol 2011;10:1108–1118.
24. Chesselet MF, Richter F, Zhu C, Magen I, Watson MB, Subramaniam SR. A progressive mouse model of Parkinson's disease: the Thy1-aSyn ("Line 61") mice. Neurotherapeutics. 2012;9:297–314.
25. Fleming SM, Tetreault NA, Mulligan CK, Hutson CB, Masliah E, Chesselet MF. Olfactory deficits in mice overexpressing human wildtype alpha-synuclein. Eur J Neurosci 2008;28:247–256.
26. Fernagut PO, Hutson CB, Fleming SM, et al. Behavioral and histopathological consequences of paraquat intoxication in mice: effects of alpha-synuclein over-expression. Synapse 2007;61:991–1001.
27. Fleming SM, Mulligan CK, Richter F, et al. A pilot trial of the microtubule-interacting peptide (NAP) in mice overexpressing alpha-synuclein shows improvement in motor function and reduction of alpha-synuclein inclusions. Mol Cell Neurosci 2011;46:597–606.
28. Richter F, Gao F, Medvedeva V, et al. Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons. Neurobiol Dis 2014;69C:263–275.
29. Lu XH, Fleming SM, Meurers B, et al. Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase K-resistant alpha-synuclein. J Neurosci 2009;29:1962–1976.
30. Watson MB, Richter F, Lee SK, et al. Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein. Exp Neurol 2012;237:318–334.
31. Efron B, Tibshirani R. Statistical data analysis in the computer age. Science 1991;253:390–395.
32. Watson JB, Hatami A, David H, et al. Alterations in corticostriatal synaptic plasticity in mice overexpressing human alpha-synuclein. Neuroscience 2009;159:501–513.
33. Wu N, Joshi PR, Cepeda C, Masliah E, Levine MS. Alpha-synuclein overexpression in mice alters synaptic communication in the corticostriatal pathway. J Neurosci Res 2010;88:1764–1776.
34. Paxinos G, Franklin KBJ. The mouse brain in stereotaxic coordinates. Academic Press, San Diego, CA, 2001.
35. Batchelor PE, Liberatore GT, Wong JY, et al. Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J Neurosci 1999;19:1708–1716.
36. Sardi SP, Clarke J, Viel C, et al. Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies. Proc Natl Acad Sci U S A 2013;110:3537–3542.
37. Sun Y, Liou B, Xu YH, et al. Ex vivo and in vivo effects of isofagomine on acid beta-glucosidase variants and substrate levels in Gaucher disease. J Biol Chem 2011;287:4275–4287.
38. Sun Y, Ran H, Liou B, et al. Isofagomine in vivo effects in a neuronopathic Gaucher disease mouse. PLoS One 2011;6:e19037.
39. Fleming S, Chesselet MF. Modeling non-motor symptoms of Parkinson’s disease in genetic mouse models. In: Groenewegen HJ, Voorn P, Berendse HW, Mulder AB, Cools AR, (eds) Basal ganglia IX. Springer, New York, 2009, pp. 483–492.
40. Lee KW, Chen W, Junn E, et al. Enhanced phosphatase activity attenuates alpha-Synucleinopathy in a mouse model. J Neurosci 2011;31:6963–6971.
41. Kramer ML, Schulz-Schaeffer WJ. Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci 2007;27:1405–1410.
42. Tompkins MM, Hill WD. Contribution of somal Lewy bodies to neuronal death. Brain Res 1997;775:24–29.
43. Schulz-Schaeffer WJ. The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia. Acta Neuropathol 2010;120:131–143.
44. Martinez-Vicente M, Talloczy Z, Kaushik S, et al. Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J Clin Invest 2008;118:777–788.