Nurr1 and retinoid X receptor ligands stimulate ret signaling in dopamine neurons and can alleviate α-synuclein disrupted gene expression

Journal of Neuroscience

Volumn 35, Issue 42, 2015, Pages 14370-14385

  Volakakis, Nikolaos ^a   Tiklova, Katarina ^a   Decressac, Mickael ^b,c   Papathanou, Maria ^a,d   Mattsson, Bengt ^b   Gillberg, Linda ^a   Nobre, André ^a   Björklund, Anders ^b   Perlmann, Thomas ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b LUND UNIVERSITY   (Sweden)

^c TELETHON INSTITUTE OF GENETICS AND MEDICINE TIGEM   (Italy)

^d UPPSALA UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; BEXAROTENE; NUCLEAR RECEPTOR RELATED FACTOR 1; RETINOID X RECEPTOR; HOMEODOMAIN PROTEIN; NR4A2 PROTEIN, MOUSE; OXIDOPAMINE; SYNAPSIN; TETRALIN DERIVATIVE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR PITX3;

ADULT; ANIMAL BEHAVIOR; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOPAMINERGIC NERVE CELL; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; MOUSE; NEUROTROPISM; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA SEQUENCE; WESTERN BLOTTING; AGONISTS; ANIMAL; ANIMAL EMBRYO; CELL CULTURE; CYTOLOGY; DRUG EFFECTS; FEMALE; GENE EXPRESSION REGULATION; GENETICS; MESENCEPHALON; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION; SPRAGUE DAWLEY RAT; STEREOTYPY; TRANSGENIC MOUSE;

ALPHA-SYNUCLEIN; ANIMALS; CELLS, CULTURED; DOPAMINERGIC NEURONS; EMBRYO, MAMMALIAN; FEMALE; GENE EXPRESSION REGULATION; HOMEODOMAIN PROTEINS; HUMANS; MESENCEPHALON; MICE; MICE, TRANSGENIC; NUCLEAR RECEPTOR SUBFAMILY 4, GROUP A, MEMBER 2; OXIDOPAMINE; RATS; RATS, SPRAGUE-DAWLEY; RETINOID X RECEPTORS; SIGNAL TRANSDUCTION; STEREOTYPED BEHAVIOR; SYNAPSINS; TETRAHYDRONAPHTHALENES; TRANSCRIPTION FACTORS;

EID: 84944936972     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.1155-15.2015     Document Type: Article

References (64)

1. Anders S, Huber W (2010) Differential expression analysis for sequence count data. Genome Biol 11:R106. CrossRef Medline
2. Anichtchik O, Calo L, Spillantini MG (2013) Synaptic dysfunction in synucleinopathies. CNS Neurol Disord Drug Targets 12:1094-1100. Medline
3. Barceló-Coblijn G, Golovko MY, Weinhofer I, Berger J, Murphy EJ (2007) Brain neutral lipids mass is increased in alpha-synuclein gene-ablated mice. J Neurochem 101:132–141. Medline
4. Bar-On P, Crews L, Koob AO, Mizuno H, Adame A, Spencer B, Masliah E (2008) Statins reduce neuronal alpha-synuclein aggregation in in vitro models of Parkinson’s disease. J Neurochem 105:1656-1667. CrossRef Medline
5. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 57:289-300.
6. Bosco DA, Fowler DM, Zhang Q, Nieva J, Powers ET, Wentworth P Jr, Lerner RA, Kelly JW (2006) Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate alpha-synuclein fibrilization. Nat Chem Biol 2:249-253. CrossRef Medline
7. Castillo SO, Baffi JS, Palkovits M, Goldstein DS, Kopin IJ, Witta J, Magnuson MA, Nikodem VM (1998) Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene. Mol Cell Neurosci 11:36–46. CrossRef Medline
8. Castro DS, Hermanson E, Joseph B, Wallén A, Aarnisalo P, Heller A, Perlmann T (2001) Induction of cell cycle arrest and morphological differentiation by Nurr1 and retinoids in dopamine MN9D cells. J Biol Chem 276:43277-43284. CrossRef Medline
9. Chu Y, Kompoliti K, Cochran EJ, Mufson EJ, Kordower JH (2002) Agerelated decreases in Nurr1 immunoreactivity in the human substantia nigra. J Comp Neurol 450:203–214. CrossRef Medline
10. Chu Y, Morfini GA, Langhamer LB, He Y, Brady ST, Kordower JH (2012) Alterations in axonal transport motor proteins in sporadic and experimental Parkinson’s disease. Brain 135:2058-2073. CrossRef Medline
11. Chung CY, Koprich JB, Hallett PJ, Isacson O (2009) Functional enhancement and protection of dopaminergic terminals by RAB3B overexpression. Proc Natl Acad Sci U S A 106:22474-22479. CrossRef Medline
12. Corona JC, de Souza SC, Duchen MR (2014) PPARgamma activation rescues mitochondrial function from inhibition of complex I and loss of PINK1. Exp Neurol 253:16-27. CrossRef Medline
13. Cramer PE, Cirrito JR, Wesson DW, Lee CY, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR, Wilson DA, Landreth GE (2012) ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. Science 335:1503–1506. CrossRef Medline
14. Decressac M, Kadkhodaei B, Mattsson B, Laguna A, Perlmann T, Björklund A (2012) alpha-Synuclein-induced down-regulation of Nurr1 disrupts GDNF signaling in nigral dopamine neurons. Sci Transl Med 4:163ra156. Medline
15. Decressac M, Volakakis N, Björklund A, Perlmann T (2013a) NURR1 in Parkinson disease–from pathogenesis to therapeutic potential. Nat Rev Neurol 9:629–636. CrossRef Medline
16. Decressac M, Mattsson B, Weikop P, Lundblad M, Jakobsson J, Björklund A (2013b) TFEB-mediated autophagy rescues midbrain dopamine neurons from alpha-synuclein toxicity. Proc Natl Acad Sci U S A 110:E1817-E1826. CrossRef Medline
17. Dignam JD, Lebovitz RM, Roeder RG (1983) Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res 11:1475–1489. CrossRef Medline
18. Duce JA, Smith DP, Blake RE, Crouch PJ, Li QX, Masters CL, Trounce IA (2006) Linker histone H1 binds to disease associated amyloid-like fibrils. J Mol Biol 361:493–505. CrossRef Medline
19. Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, Crowley C, Yocum RC (2001) Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol 19:2456-2471. Medline
20. Exner N, Lutz AK, Haass C, Winklhofer KF (2012) Mitochondrial dysfunction in Parkinson’s disease: molecular mechanisms and pathophysiological consequences. EMBO J 31:3038-3062. CrossRef Medline
21. Forman BM, Umesono K, Chen J, Evans RM (1995) Unique response pathways are established by allosteric interactions among nuclear hormone receptors. Cell 81:541–550. Medline
22. Games D, Seubert P, Rockenstein E, Patrick C, Trejo M, Ubhi K, Ettle B, Ghassemiam M, Barbour R, Schenk D, Nuber S, Masliah E (2013) Axonopathy in an alpha-synuclein transgenic model of Lewy body disease is associated with extensive accumulation of C-terminal-truncated alphasynuclein. Am J Pathol 182:940-953. CrossRef Medline
23. Gilardi F, Desvergne B (2014) RXRs: collegial partners. Subcell Biochem 70:75–102. CrossRef Medline
24. Goers J, Manning-Bog AB, McCormack AL, Millett IS, Doniach S, Di Monte DA, Uversky VN, Fink AL (2003) Nuclear localization of alphasynuclein and its interaction with histones. Biochemistry 42:8465-8471. CrossRef Medline
25. Halliday GM, Ophof A, Broe M, Jensen PH, Kettle E, Fedorow H, Cartwright MI, Griffiths FM, Shepherd CE, Double KL (2005) Alpha-synuclein redistributes to neuromelanin lipid in the substantia nigra early in Parkinson’s disease. Brain 128:2654-2664. CrossRef Medline
26. Hegde ML, Rao KS (2007) DNA induces folding in alpha-synuclein: understanding the mechanism using chaperone property of osmolytes. Arch Biochem Biophys 464:57-69. CrossRef Medline
27. Huang da W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44-57. Medline
28. Jin H, Kanthasamy A, Ghosh A, Yang Y, Anantharam V, Kanthasamy AG (2011) alpha-Synuclein negatively regulates protein kinase Cdelta expression to suppress apoptosis in dopaminergic neurons by reducing p300 histone acetyltransferase activity. J Neurosci 31:2035–2051. CrossRef Medline
29. Jin J, Li GJ, Davis J, Zhu D, Wang Y, Pan C, Zhang J (2007) Identification of novel proteins associated with both alpha-synuclein and DJ-1. Mol Cell Proteomics 6:845-859. Medline
30. Kadkhodaei B, Ito T, Joodmardi E, Mattsson B, Rouillard C, Carta M, Muramatsu S, Sumi-Ichinose C, Nomura T, Metzger D, Chambon P, Lindqvist E, Larsson NG, Olson L, Björklund A, Ichinose H, Perlmann T (2009) Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons. J Neurosci 29:15923–15932. CrossRef Medline
31. Kadkhodaei B, Alvarsson A, Schintu N, Ramsköld D, Volakakis N, Joodmardi E, Yoshitake T, Kehr J, Decressac M, Björklund A, Sandberg R, Svenningsson P, Perlmann T (2013) Transcription factor Nurr1 maintains fiber integrity and nuclear encoded mitochondrial gene expression in dopamine neurons. Proc Natl Acad Sci U S A 110:2360-2365. CrossRef Medline
32. Klein P, Müller-Rischart AK, Motori E, Schönbauer C, Schnorrer F, Winklhofer KF, Klein R (2014) Ret rescues mitochondrial morphology and muscle degeneration of Drosophila Pink1 mutants. EMBO J 33:341–355. CrossRef Medline
33. Kontopoulos E, Parvin JD, Feany MB (2006) Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet 15:3012–3023. CrossRef Medline
34. Lee HJ, Khoshaghideh F, Lee S, Lee SJ (2006) Impairment of microtubuledependent trafficking by overexpression of alpha-synuclein. Eur J Neurosci 24:3153–3162. CrossRef Medline
35. Lees AJ, Hardy J, Revesz T (2009) Parkinson’s disease. Lancet 373:2055-2066. CrossRef Medline
36. Lin X, Parisiadou L, Sgobio C, Liu G, Yu J, Sun L, Shim H, Gu XL, Luo J, Long CX, Ding J, Mateo Y, Sullivan PH, Wu LG, Goldstein DS, Lovinger D, Cai H (2012) Conditional expression of Parkinson’s disease-related mutant alpha-synuclein in the midbrain dopaminergic neurons causes progressive neurodegeneration and degradation of transcription factor nuclear receptor related 1. J Neurosci 32:9248-9264. CrossRef Medline
37. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402-408. CrossRef Medline
38. Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550. CrossRef Medline
39. Maroteaux L, Campanelli JT, Scheller RH (1988) Synuclein: a neuronspecific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8:2804-2815. Medline
40. McFarland K, Spalding TA, Hubbard D, Ma JN, Olsson R, Burstein ES (2013) Low dose bexarotene treatment rescues dopamine neurons and restores behavioral function in models of Parkinson’s disease. ACS Chem Neurosci 4:1430-1438. CrossRef Medline
41. Mijatovic J, Piltonen M, Alberton P, Männistö PT, Saarma M, Piepponen TP (2011) Constitutive Ret signaling is protective for dopaminergic cell bodies but not for axonal terminals. Neurobiol Aging 32:1486-1494. CrossRef Medline
42. Monti B, Gatta V, Piretti F, Raffaelli SS, Virgili M, Contestabile A (2010) Valproic acid is neuroprotective in the rotenone rat model of Parkinson’s disease: involvement of alpha-synuclein. Neurotox Res 17:130-141. CrossRef Medline
43. Moran LB, Croisier E, Duke DC, Kalaitzakis ME, Roncaroli F, Deprez M, Dexter DT, Pearce RK, Graeber MB (2007) Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra. Acta Neuropathol 113:253–263. CrossRef Medline
44. O’Donnell KC, Lulla A, Stahl MC, Wheat ND, Bronstein JM, Sagasti A (2014) Axon degeneration and PGC-1alpha-mediated protection in a zebrafish model of alpha synuclein toxicity. Dis Model Mech 7:571–582. CrossRef Medline
45. Ono K, Ikemoto M, Kawarabayashi T, Ikeda M, Nishinakagawa T, Hosokawa M, Shoji M, Takahashi M, Nakashima M (2009) A chemical chaperone, sodium 4 phenylbutyric acid, attenuates the pathogenic potency in human alpha-synuclein A30P + A53T transgenic mice. Parkinsonism Relat Disord 15:649–654. CrossRef Medline
46. Perlmann T, Jansson L (1995) A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. Genes Dev 9:769-782. CrossRef Medline
47. Picelli S, Björklund ÅK, Faridani OR, Sagasser S, Winberg G, Sandberg R (2013) Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat Methods 10:1096-1098. CrossRef Medline
48. Prots I, Veber V, Brey S, Campioni S, Buder K, Riek R, Böhm KJ, Winner B (2013) alpha-Synuclein oligomers impair neuronal microtubule-kinesin interplay. J Biol Chem 288:21742–21754. CrossRef Medline
49. Ravnskjaer K, Frigerio F, Boergesen M, Nielsen T, Maechler P, Mandrup S (2010) PPARdelta is a fatty acid sensor that enhances mitochondrial oxidation in insulin secreting cells and protects against fatty acid-induced dysfunction. J Lipid Res 51:1370-1379. CrossRef Medline
50. Reiner DJ, Yu SJ, Shen H, He Y, Bae E, Wang Y (2014) 9-Cis retinoic acid protects against methamphetamine-induced neurotoxicity in nigrostriatal dopamine neurons. Neurotox Res 25:248-261. CrossRef Medline
51. Saucedo-Cardenas O, Quintana-Hau JD, Le WD, Smidt MP, Cox JJ, De Mayo F, Burbach JP, Conneely OM (1998) Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci U S A 95:4013-4018. CrossRef Medline
52. Siebert H, Kahle PJ, Kramer ML, Isik T, Schlüter OM, Schulz-Schaeffer WJ, Brück W (2010) Overexpression of alpha-synuclein in the nervous system enhances axonal degeneration after peripheral nerve lesion in a transgenic mouse strain. J Neurochem 114:1007–1018. Medline
53. Smidt MP, Burbach JP (2007) How to make a mesodiencephalic dopaminergic neuron. Nat Rev Neurosci 8:21–32. CrossRef Medline
54. Smith Y, Wichmann T, Factor SA, DeLong MR (2012) Parkinson’s disease therapeutics: new developments and challenges since the introduction of levodopa. Neuropsychopharmacology 37:213–246. CrossRef Medline
55. Specht CG, Tigaret CM, Rast GF, Thalhammer A, Rudhard Y, Schoepfer R (2005) Subcellular localisation of recombinant alpha- and gammasynuclein. Mol Cell Neurosci 28:326-334. CrossRef Medline
56. Ungerstedt U, Arbuthnott GW (1970) Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res 24:485-493. CrossRef Medline
57. Wang Z, Benoit G, Liu J, Prasad S, Aarnisalo P, Liu X, Xu H, Walker NP, Perlmann T (2003) Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors. Nature 423:555–560. CrossRef Medline
58. Yin LH, Shen H, Diaz-Ruiz O, Bäckman CM, Bae E, Yu SJ, Wang Y (2012) Early post-treatment with 9-cis retinoic acid reduces neurodegeneration of dopaminergic neurons in a rat model of Parkinson’s disease. BMC Neurosci 13:120. CrossRef Medline
59. Yu S, Li X, Liu G, Han J, Zhang C, Li Y, Xu S, Liu C, Gao Y, Yang H, Uéda K, Chan P (2007) Extensive nuclear localization of alpha-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody. Neuroscience 145:539-555. CrossRef Medline
60. Zetterström RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T (1997) Dopamine neuron agenesis in Nurr1-deficient mice. Science 276: 248–250. CrossRef Medline
61. Zhao S, Maxwell S, Jimenez-Beristain A, Vives J, Kuehner E, Zhao J, O’Brien C, de Felipe C, Semina E, Li M (2004) Generation of embryonic stem cells and transgenic mice expressing green fluorescence protein in midbrain dopaminergic neurons. Eur J Neurosci 19:1133–1140. CrossRef Medline
62. Zhou W, Bercury K, Cummiskey J, Luong N, Lebin J, Freed CR (2011) Phenylbutyrate up-regulates the DJ-1 protein and protects neurons in cell culture and in animal models of Parkinson disease. J Biol Chem 286: 14941–14951. CrossRef Medline
63. Zhou Y, Gu G, Goodlett DR, Zhang T, Pan C, Montine TJ, Montine KS, Aebersold RH, Zhang J (2004) Analysis of alpha-synuclein-associated proteins by quantitative proteomics. J Biol Chem 279:39155–39164. CrossRef Medline
64. Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D (1997) Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 15:871-875. CrossRef Medline