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The Cerebellum

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01.09.2009

Friedreich’s Ataxia: From the (GAA)_n Repeat Mediated Silencing to New Promising Molecules for Therapy

verfasst von: Daniele Marmolino, Fabio Acquaviva

Erschienen in: The Cerebellum | Ausgabe 3/2009

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Abstract

Friedreich’s ataxia (FRDA) is a neurodegenerative disease due to a pathological expansion of a GAA triplet repeat in the first intron of the FXN gene encoding for the mitochondrial protein frataxin. The expansion is responsible for most cases of FRDA through the formation of a nonusual B-DNA structure and heterochromatin conformation that determine a direct transcriptional silencing and the subsequent reduction in frataxin expression. Among other functions, frataxin is an iron chaperone central for the assembly of iron–sulfur clusters in mitochondria; its reduction is associated with iron accumulation in mitochondria, increased cellular sensitivity to oxidative stress and cell damage. There is, nowadays, no effective therapy for FRDA and current therapeutic strategies mainly act to slow down the consequences of frataxin deficiency. Therefore, drugs that are able to increase the amount of frataxin are excellent candidates for a rational approach to FRDA therapy. Recently, several drugs have been assessed for their ability to increase the amount of cellular frataxin, including human recombinant erythropoietin, histone deacetylase inhibitors, and the PPAR-γ agonists.

Delatycki M, Williamson R, Forrest S (2000) Friedreich ataxia: an overview. J Med Genet 37(1):1–8PubMed

Finocchiaro G, Baio G, Micossi P, Pozza G, di Donato S (1988) Glucose metabolism alterations in Friedreich’s ataxia. Neurology 38(8):1292–1296PubMed

Filla A, De Michele G, Coppola G, Federico A, Vita G, Toscano A et al (2000) Accuracy of clinical diagnostic criteria for Friedreich’s ataxia. Mov Disord 15(6):1255–1258PubMed

Pandolfo M (2003) Friedreich ataxia. Semin Pediatr Neurol 10(3):163–172PubMed

Filla A, DeMichele G, Caruso G, Marconi R, Campanella G (1990) Genetic data and natural history of Friedreich’s disease: a study of 80 Italian patients. J Neurol 237(6):345–351PubMed

Shapcott D, Melancon S, Butterworth R, Khoury K, Collu R, Breton G et al (1976) Glucose and insulin metabolism in Friedreich’s ataxia. Can J Neurol Sci 3(4):361–364PubMed

Campuzano V, Montermini L, Moltò M, Pianese L, Cossée M, Cavalcanti F et al (1996) Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271(5254):1423–1427PubMed

Campuzano V, Montermini L, Lutz Y, Cova L, Hindelang C, Jiralerspong S et al (1997) Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Genet 6(11):1771–1780PubMed

Kostrzewa M, Klockgether T, Damian M, Müller U (1997) Locus heterogeneity in Friedreich ataxia. Neurogenetics 1(1):43–47PubMed

10.

Koutnikova H, Campuzano V, Foury F, Dollé P, Cazzalini O, Koenig M (1997) Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin. Nat Genet 16(4):345–351PubMed

11.

Bidichandani S, Ashizawa T, Patel P (1997) Atypical Friedreich ataxia caused by compound heterozygosity for a novel missense mutation and the GAA triplet-repeat expansion. Am J Hum Genet 60(5):1251–1256PubMed

12.

Orr H, Zoghbi H (2007) Trinucleotide repeat disorders. Annu Rev Neurosci 30:575–621PubMed

13.

Pianese L, Turano M, Lo Casale M, De Biase I, Giacchetti M, Monticelli A et al (2004) Real time PCR quantification of frataxin mRNA in the peripheral blood leucocytes of Friedreich ataxia patients and carriers. J Neurol Neurosurg Psychiatry 75(7):1061–1063PubMed

14.

Lodi R, Cooper JM, Bradley JL, Manners D, Styles P, Taylor DJ, Schapira AH (1999) Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia. Proc Natl Acad Sci U S A 96:11492–11495PubMed

15.

Askwith C, Eide D, Van Ho A, Bernard PS, Li L, Davis-Kaplan S, Sipe DM, Kaplan J (1994) The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake. Cell 76(2):403–410PubMed

16.

Stearman R, Yuan DS, Yamaguchi-Iwai Y, Klausner RD, Dancis A (1996) A permease–oxidase complex involved in high-affinity iron uptake in yeast. Science 271(5255):1552–1557PubMed

17.

Pandolfo M (2006) Iron and Friedreich ataxia. J Neural Transm Suppl 70:143–146PubMed

18.

Geoffroy G, Barbeau A, Breton G, Lemieux B, Aube M, Leger C et al (1976) Clinical description and roentgenologic evaluation of patients with Friedreich’s ataxia. Can J Neurol Sci 3(4):279–286PubMed

19.

Harding A (1981) Friedreich’s ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 104(3):589–620PubMed

20.

Klockgether T, Chamberlain S, Wüllner U, Fetter M, Dittmann H, Petersen D et al (1993) Late-onset Friedreich’s ataxia. Molecular genetics, clinical neurophysiology, and magnetic resonance imaging. Arch Neurol 50(8):803–806PubMed

21.

Dürr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C et al (1996) Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N Engl J Med 335(16):1169–1175PubMed

22.

Lamont P, Davis M, Wood N (1997) Identification and sizing of the GAA trinucleotide repeat expansion of Friedreich’s ataxia in 56 patients. Clinical and genetic correlates. Brain 120(Pt 4):673–680PubMed

23.

Schöls L, Amoiridis G, Przuntek H, Frank G, Epplen J, Epplen C (1997) Friedreich’s ataxia. Revision of the phenotype according to molecular genetics. Brain 120(Pt 12):2131–2140PubMed

24.

Ohshima K, Montermini L, Wells R, Pandolfo M (1998) Inhibitory effects of expanded GAA.TTC triplet repeats from intron I of the Friedreich ataxia gene on transcription and replication in vivo. J Biol Chem 273(23):14588–14595PubMed

25.

Bidichandani S, Ashizawa T, Patel P (1998) The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. Am J Hum Genet 62(1):111–121PubMed

26.

Sakamoto N, Chastain P, Parniewski P, Ohshima K, Pandolfo M, Griffith J et al (1999) Sticky DNA: self-association properties of long GAA.TTC repeats in R.R.Y triplex structures from Friedreich’s ataxia. Mol Cell 3(4):465–475PubMed

27.

Sakamoto N, Ohshima K, Montermini L, Pandolfo M, Wells R (2001) Sticky DNA, a self-associated complex formed at long GAA*TTC repeats in intron 1 of the frataxin gene, inhibits transcription. J Biol Chem 276(29):27171–27177PubMed

28.

Wells R (2008) DNA triplexes and Friedreich ataxia. FASEB J 22(6):1625–1634PubMed

29.

Grabczyk E, Usdin K (2000) Alleviating transcript insufficiency caused by Friedreich’s ataxia triplet repeats. Nucleic Acids Res 28(24):4930–4937PubMed

30.

Grabczyk E, Mancuso M, Sammarco M (2007) A persistent RNA.DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro. Nucleic Acids Res 35(16):5351–5359PubMed

31.

Saveliev A, Everett C, Sharpe T, Webster Z, Festenstein R (2003) DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing. Nature 422(6934):909–913PubMed

32.

Grabczyk E, Kumari D, Usdin K (2001) Fragile X syndrome and Friedreich’s ataxia: two different paradigms for repeat induced transcript insufficiency. Brain Res Bull 56(3–4):367–373PubMed

33.

Stewart M, Li J, Wong J (2005) Relationship between histone H3 lysine 9 methylation, transcription repression, and heterochromatin protein 1 recruitment. Mol Cell Biol 25(7):2525–2538PubMed

34.

Kernochan L, Russo M, Woodling N, Huynh T, Avila A, Fischbeck K et al (2005) The role of histone acetylation in SMN gene expression. Hum Mol Genet 14(9):1171–1182PubMed

35.

Langley B, Gensert J, Beal M, Ratan R (2005) Remodeling chromatin and stress resistance in the central nervous system: histone deacetylase inhibitors as novel and broadly effective neuroprotective agents. Curr Drug Targets CNS Neurol Disord 4(1):41–50PubMed

36.

Cho D, Thienes C, Mahoney S, Analau E, Filippova G, Tapscott S (2005) Antisense transcription and heterochromatin at the DM1 CTG repeats are constrained by CTCF. Mol Cell 20(3):483–489PubMed

37.

Tapscott S, Klesert T, Widrow R, Stöger R, Laird C (1998) Fragile-X syndrome and myotonic dystrophy: parallels and paradoxes. Curr Opin Genet Dev 8(2):245–253PubMed

38.

Herman D, Jenssen K, Burnett R, Soragni E, Perlman S, Gottesfeld J (2006) Histone deacetylase inhibitors reverse gene silencing in Friedreich’s ataxia. Nat Chem Biol 2(10):551–558PubMed

39.

Gottesfeld J (2007) Small molecules affecting transcription in Friedreich ataxia. Pharmacol Ther 116(2):236–248PubMed

40.

Elgin S, Grewal S (2003) Heterochromatin: silence is golden. Curr Biol 13(23):R895–R898PubMed

41.

Miranda C, Santos M, Ohshima K, Smith J, Li L, Bunting M et al (2002) Frataxin knockin mouse. FEBS Lett 512(1–3):291–297PubMed

42.

Rai M, Soragni E, Jenssen K, Burnett R, Herman D, Coppola G et al (2008) HDAC inhibitors correct frataxin deficiency in a Friedreich ataxia mouse model. PLoS ONE 3(4):e1958PubMed

43.

Greene E, Mahishi L, Entezam A, Kumari D, Usdin K (2007) Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia. Nucleic Acids Res 35(10):3383–3390PubMed

44.

El-Osta A, Wolffe A (2000) DNA methylation and histone deacetylation in the control of gene expression: basic biochemistry to human development and disease. Gene Expr 9(1–2):63–75PubMed

45.

Castaldo I, Pinelli M, Monticelli A, Acquaviva F, Giacchetti M, Filla A et al (2008) DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich’s ataxia patients. J Med Genet 45:808–812

46.

Al-Mahdawi S, Pinto R, Ismail O, Varshney D, Lymperi S, Sandi C et al (2008) The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues. Hum Mol Genet 17(5):735–746PubMed

47.

Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L et al (1997) Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 276(5319):1709–1712PubMed

48.

Foury F, Cazzalini O (1997) Deletion of the yeast homologue of the human gene associated with Friedreich’s ataxia elicits iron accumulation in mitochondria. FEBS Lett 411(2–3):373–377PubMed

49.

Schoenfeld R, Napoli E, Wong A, Zhan S, Reutenauer L, Morin D et al (2005) Frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells. Hum Mol Genet 14(24):3787–3799PubMed

50.

Stehling O, Elsässer H, Brückel B, Mühlenhoff U, Lill R (2004) Iron–sulfur protein maturation in human cells: evidence for a function of frataxin. Hum Mol Genet 3(23):3007–3015

51.

Ramazzotti A, Vanmansart V, Foury F (2004) Mitochondrial functional interactions between frataxin and Isu1p, the iron–sulfur cluster scaffold protein, in Saccharomyces cerevisiae. FEBS Lett 557(1–3):215–220PubMed

52.

Yoon T, Cowan J (2003) Iron–sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe–2S] clusters in ISU-type proteins. J Am Chem Soc 125(20):6078–6084PubMed

53.

Yoon T, Cowan J (2004) Frataxin-mediated iron delivery to ferrochelatase in the final step of heme biosynthesis. J Biol Chem 279(25):25943–25946PubMed

54.

Zhang Y, Lyver E, Knight S, Lesuisse E, Dancis A (2005) Frataxin and mitochondrial carrier proteins, Mrs3p and Mrs4p, cooperate in providing iron for heme synthesis. J Biol Chem 280(20):19794–19807PubMed

55.

Mühlenhoff U, Gerber J, Richhardt N, Lill R (2003) Components involved in assembly and dislocation of iron–sulfur clusters on the scaffold protein Isu1p. EMBO J 22(18):4815–4825PubMed

56.

Park S, Gakh O, O’Neill H, Mangravita A, Nichol H, Ferreira G et al (2003) Yeast frataxin sequentially chaperones and stores iron by coupling protein assembly with iron oxidation. J Biol Chem 278(33):31340–31351PubMed

57.

Gakh O, Adamec J, Gacy A, Twesten R, Owen W, Isaya G (2002) Physical evidence that yeast frataxin is an iron storage protein. Biochemistry 41(21):6798–6804PubMed

58.

Gakh O, Park S, Liu G, Macomber L, Imlay J, Ferreira G et al (2006) Mitochondrial iron detoxification is a primary function of frataxin that limits oxidative damage and preserves cell longevity. Hum Mol Genet 15(3):467–479PubMed

59.

O’Neill H, Gakh O, Park S, Cui J, Mooney S, Sampson M et al (2005) Assembly of human frataxin is a mechanism for detoxifying redox-active iron. Biochemistry 44(2):537–545PubMed

60.

Karlberg T, Schagerlöf U, Gakh O, Park S, Ryde U, Lindahl M et al (2006) The structures of frataxin oligomers reveal the mechanism for the delivery and detoxification of iron. Structure 14(10):1535–1546PubMed

61.

Adamec J, Rusnak F, Owen W, Naylor S, Benson L, Gacy A et al (2000) Iron-dependent self-assembly of recombinant yeast frataxin: implications for Friedreich ataxia. Am J Hum Genet 67(3):549–562PubMed

62.

Chantrel-Groussard K, Geromel V, Puccio H, Koenig M, Munnich A, Rötig A et al (2001) Disabled early recruitment of antioxidant defenses in Friedreich’s ataxia. Hum Mol Genet 10(19):2061–2067PubMed

63.

Karthikeyan G, Lewis L, Resnick M (2002) The mitochondrial protein frataxin prevents nuclear damage. Hum Mol Genet 11(11):1351–1362PubMed

64.

Karthikeyan G, Santos J, Graziewicz M, Copeland W, Isaya G, Van Houten B et al (2003) Reduction in frataxin causes progressive accumulation of mitochondrial damage. Hum Mol Genet 12(24):3331–3342PubMed

65.

Wong A, Yang J, Cavadini P, Gellera C, Lonnerdal B, Taroni F et al (1999) The Friedreich’s ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis. Hum Mol Genet 8(3):425–430PubMed

66.

Cavadini P, Adamec J, Taroni F, Gakh O, Isaya G (2000) Two-step processing of human frataxin by mitochondrial processing peptidase. Precursor and intermediate forms are cleaved at different rates. J Biol Chem 275(52):41469–41475PubMed

67.

Yoon T, Dizin E, Cowan J (2007) N-terminal iron-mediated self-cleavage of human frataxin: regulation of iron binding and complex formation with target proteins. J Biol Inorg Chem 12(4):535–542PubMed

68.

Condò I, Ventura N, Malisan F, Rufini A, Tomassini B, Testi R (2007) In vivo maturation of human frataxin. Hum Mol Genet 16(13):1534–1540PubMed

69.

Babady N, Pang Y, Elpeleg O, Isaya G (2007) Cryptic proteolytic activity of dihydrolipoamide dehydrogenase. Proc Natl Acad Sci U S A 104(15):6158–6163PubMed

70.

Acquaviva F, De Biase I, Nezi L, Ruggiero G, Tatangelo F, Pisano C et al (2005) Extra-mitochondrial localisation of frataxin and its association with IscU1 during enterocyte-like differentiation of the human colon adenocarcinoma cell line Caco-2. J Cell Sci 118(Pt 17):3917–3924PubMed

71.

Condò I, Ventura N, Malisan F, Tomassini B, Testi R (2006) A pool of extramitochondrial frataxin that promotes cell survival. J Biol Chem 281(24):16750–16756PubMed

72.

O’Neill H, Gakh O, Isaya G (2005) Supramolecular assemblies of human frataxin are formed via subunit–subunit interactions mediated by a non-conserved amino-terminal region. J Mol Biol 345(3):433–439PubMed

73.

Napoli E, Taroni F, Cortopassi G (2006) Frataxin, iron–sulfur clusters, heme, ROS, and aging. Antioxid Redox Signal 8(3–4):506–516PubMed

74.

González-Cabo P, Vázquez-Manrique R, García-Gimeno M, Sanz P, Palau F (2005) Frataxin interacts functionally with mitochondrial electron transport chain proteins. Hum Mol Genet 14(15):2091–2098PubMed

75.

Blanquart C, Barbier O, Fruchart J, Staels B, Glineur C (2003) Peroxisome proliferator-activated receptors: regulation of transcriptional activities and roles in inflammation. J Steroid Biochem Mol Biol 85(2–5):267–273PubMed

76.

Torchia J, Rose D, Inostroza J, Kamei Y, Westin S, Glass C et al (1997) The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature 387(6634):677–684. JunPubMed

77.

Kelly D, Scarpulla R (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18(4):357–368PubMed

78.

Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V et al (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98(1):115–124PubMed

79.

St-Pierre J, Drori S, Uldry M, Silvaggi J, Rhee J, Jäger S et al (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127(2):397–408PubMed

80.

Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E et al (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267–273PubMed

81.

Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R et al (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 100:8466–8471PubMed

82.

Soyal S, Krempler F, Oberkofler H, Patsch W (2006) PGC-1alpha: a potent transcriptional cofactor involved in the pathogenesis of type 2 diabetes. Diabetologia 49:1477–1488PubMed

83.

Wilson RB (2006) Experimental therapeutics for Friedreich ataxia. In: Wells RD, Warren ST, Sarmiento M (eds) Genetic instabilities and neurological diseases, 2nd edn. Academic, San Diego, p 766

84.

Sugiyama Y, Fujita T, Matsumoto M, Okamoto K, Imada I (1985) Effects of idebenone (CV-2619) and its metabolites on respiratory activity and lipid peroxidation in brain mitochondria from rats and dogs. J Pharmacobiodyn 8(12):1006–1017PubMed

85.

Rustin P, von Kleist-Retzow J, Chantrel-Groussard K, Sidi D, Munnich A, Rötig A (1999) Effect of idebenone on cardiomyopathy in Friedreich’s ataxia: a preliminary study. Lancet 354(9177):477–479PubMed

86.

Di Prospero N, Baker A, Jeffries N, Fischbeck K (2007) Neurological effects of high-dose idebenone in patients with Friedreich’s ataxia: a randomised, placebo-controlled trial. Lancet Neurol 6(10):878–886PubMed

87.

Stephens N, Parsons A, Schofield P, Kelly F, Cheeseman K, Mitchinson M (1996) Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347(9004):781–786PubMed

88.

Shoulson I (1998) DATATOP: a decade of neuroprotective inquiry. Parkinson Study Group. Deprenyl and tocopherol antioxidative therapy of Parkinsonism. Ann Neurol 44(3 Suppl 1):S160–S166PubMed

89.

Bostick R, Potter J, McKenzie D, Sellers T, Kushi L, Steinmetz K et al (1993) Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women’s Health Study. Cancer Res 53(18):4230–4237PubMed

90.

Musumeci O, Naini A, Slonim A, Skavin N, Hadjigeorgiou G, Krawiecki N et al (2001) Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology 56(7):849–855PubMed

91.

Cooper J, Schapira A (2007) Friedreich’s ataxia: coenzyme Q10 and vitamin E therapy. Mitochondrion 7(Suppl):S127–S135PubMed

92.

Hart P, Lodi R, Rajagopalan B, Bradley J, Crilley J, Turner C et al (2005) Antioxidant treatment of patients with Friedreich ataxia: four-year follow-up. Arch Neurol 62(4):621–626PubMed

93.

Hausse A, Aggoun Y, Bonnet D, Sidi D, Munnich A, Rötig A et al (2002) Idebenone and reduced cardiac hypertrophy in Friedreich’s ataxia. Heart 87(4):346–349PubMed

94.

Buyse G, Mertens L, Di Salvo G, Matthijs I, Weidemann F, Eyskens B et al (2003) Idebenone treatment in Friedreich’s ataxia: neurological, cardiac, and biochemical monitoring. Neurology 60(10):1679–1681PubMed

95.

Pineda M, Arpa J, Montero R, Aracil A, Domínguez F, Galván M et al (2008) Idebenone treatment in paediatric and adult patients with Friedreich ataxia: long-term follow-up. Eur J Paediatr Neurol 12(6):470–475PubMed

96.

Kelso G, Porteous C, Coulter C, Hughes G, Porteous W, Ledgerwood E et al (2001) Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chem 276(7):4588–4596PubMed

97.

Smith R, Porteous C, Gane A, Murphy M (2003) Delivery of bioactive molecules to mitochondria in vivo. Proc Natl Acad Sci U S A 100(9):5407–5412PubMed

98.

Kalinowski D, Richardson D (2005) The evolution of iron chelators for the treatment of iron overload disease and cancer. Pharmacol Rev 57(4):547–583PubMed

99.

Richardson D, Mouralian C, Ponka P, Becker E (2001) Development of potential iron chelators for the treatment of Friedreich’s ataxia: ligands that mobilize mitochondrial iron. Biochim Biophys Acta 1536(2–3):133–140PubMed

100.

Waldvogel D, van Gelderen P, Hallett M (1999) Increased iron in the dentate nucleus of patients with Friedrich’s ataxia. Ann Neurol 46(1):123–125PubMed

101.

Wilson R (2006) Iron dysregulation in Friedreich ataxia. Semin Pediatr Neurol 13(3):166–175PubMed

102.

Richardson D (2003) Friedreich’s ataxia: iron chelators that target the mitochondrion as a therapeutic strategy? Expert Opin Investig Drugs 12(2):235–245PubMedCrossRef

103.

Boddaert N, Le Quan Sang K, Rötig A, Leroy-Willig A, Gallet S, Brunelle F et al (2007) Selective iron chelation in Friedreich ataxia: biologic and clinical implications. Blood 110(1):401–408PubMed

104.

Sohn Y, Breuer W, Munnich A, Cabantchik Z (2008) Redistribution of accumulated cell iron: a modality of chelation with therapeutic implications. Blood 111(3):1690–1699PubMed

105.

Li K, Besse E, Ha D, Kovtunovych G, Rouault T (2008) Iron-dependent regulation of frataxin expression: implications for treatment of Friedreich ataxia. Hum Mol Genet 17(15):2265–2273PubMed

106.

Goncalves S, Paupe V, Dassa E, Rustin P (2008) Deferiprone targets aconitase: implication for Friedreich’s ataxia treatment. BMC Neurol 8:20PubMed

107.

Drummond D, Noble C, Kirpotin D, Guo Z, Scott G, Benz C (2005) Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol 45:495–528PubMed

108.

Di Prospero N, Fischbeck K (2005) Therapeutics development for triplet repeat expansion diseases. Nat Rev Genet 6(10):756–765PubMed

109.

Riessland M, Brichta L, Hahnen E, Wirth B (2006) The benzamide M344, a novel histone deacetylase inhibitor, significantly increases SMN2 RNA/protein levels in spinal muscular atrophy cells. Hum Genet 120(1):101–110PubMed

110.

Sarsero J, Li L, Wardan H, Sitte K, Williamson R, Ioannou P (2003) Upregulation of expression from the FRDA genomic locus for the therapy of Friedreich ataxia. J Gene Med 5(1):72–81PubMed

111.

Morishita E, Masuda S, Nagao M, Yasuda Y, Sasaki R (1997) Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death. Neuroscience 76(1):105–116PubMed

112.

Brines M, Ghezzi P, Keenan S, Agnello D, de Lanerolle N, Cerami C et al (2000) Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A 97(19):10526–10531PubMed

113.

Xenocostas A, Cheung W, Farrell F, Zakszewski C, Kelley M, Lutynski A et al (2005) The pharmacokinetics of erythropoietin in the cerebrospinal fluid after intravenous administration of recombinant human erythropoietin. Eur J Clin Pharmacol 61(3):189–195PubMed

114.

Sakanaka M, Wen T, Matsuda S, Masuda S, Morishita E, Nagao M et al (1998) In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci U S A 95(8):4635–4640PubMed

115.

Sirén A, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P et al (2001) Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci U S A 98(7):4044–4049PubMed

116.

Bogoyevitch M (2004) An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection. Cardiovasc Res 63(2):208–216PubMed

117.

Sturm B, Stupphann D, Kaun C, Boesch S, Schranzhofer M, Wojta J et al (2005) Recombinant human erythropoietin: effects on frataxin expression in vitro. Eur J Clin Invest 35(11):711–717PubMed

118.

Acquaviva F, Castaldo I, Filla A, Giacchetti M, Marmolino D, Monticelli A et al (2008) Recombinant human erythropoietin increases frataxin protein expression without increasing mRNA expression. Cerebellum 7(3):360–365PubMed

119.

Boesch S, Sturm B, Hering S, Goldenberg H, Poewe W, Scheiber-Mojdehkar B (2007) Friedreich’s ataxia: clinical pilot trial with recombinant human erythropoietin. Ann Neurol 62(5):521–524PubMed

120.

Richter B, Bandeira-Echtler E, Bergerhoff K, Clar C, Ebrahim S (2006) Pioglitazone for type 2 diabetes mellitus. Cochrane Database Syst Rev (4):CD006060

121.

Richter B, Bandeira-Echtler E, Bergerhoff K, Clar C, Ebrahim S (2007) Rosiglitazone for type 2 diabetes mellitus. Cochrane Database Syst Rev (3):CD006063

122.

Heneka M, Landreth G (2007) PPARs in the brain. Biochim Biophys Acta 1771(8):1031–1045PubMed

123.

Heneka M, Landreth G, Hüll M (2007) Drug insight: effects mediated by peroxisome proliferator-activated receptor-gamma in CNS disorders. Nat Clin Pract Neurol 3(9):496–504PubMed

124.

Del Gaizo V, Payne R (2003) A novel TAT-mitochondrial signal sequence fusion protein is processed, stays in mitochondria, and crosses the placenta. Mol Ther 7(6):720–730PubMed

125.

Del Gaizo V, MacKenzie J, Payne R (2003) Targeting proteins to mitochondria using TAT. Mol Genet Metab 80(1–2):170–180PubMed

126.

Marmolino D, Acquaviva F, Pinelli M, Monticelli A, Castaldo I, Filla A, Cocozza S (2008) PPAR-gamma agonist azelaoyl PAF increases frataxin protein and mRNA expression. New implications for the Friedreich’s ataxia theraphy. Cerebellum. Dec. 23 (PMID: 19104905)PubMed

Titel: Friedreich’s Ataxia: From the (GAA) n Repeat Mediated Silencing to New Promising Molecules for Therapy
verfasst von: Daniele Marmolino
Fabio Acquaviva
Publikationsdatum: 01.09.2009
Verlag: Springer-Verlag
Erschienen in: The Cerebellum / Ausgabe 3/2009
Print ISSN: 1473-4222
Elektronische ISSN: 1473-4230
DOI: https://doi.org/10.1007/s12311-008-0084-2

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