Diapause Formation and Downregulation of Insulin-Like Signaling via DAF-16/FOXO Delays Axonal Degeneration and Neuronal Loss

English version České info

Axonal degeneration is a key event in the pathogenesis of neurodegenerative conditions. We show here that mec-4d triggered axonal degeneration of Caenorhabditis elegans neurons and mammalian axons share mechanistical similarities, as both are rescued by inhibition of calcium increase, mitochondrial dysfunction, and NMNAT overexpression. We then explore whether reactive oxygen species (ROS) participate in axonal degeneration and neuronal demise. C. elegans dauers have enhanced anti-ROS systems, and dauer mec-4d worms are completely protected from axonal degeneration and neuronal loss. Mechanistically, downregulation of the Insulin/IGF-1-like signaling (IIS) pathway protects neurons from degenerating in a DAF-16/FOXO–dependent manner and is related to superoxide dismutase and catalase-increased expression. Caloric restriction and systemic antioxidant treatment, which decrease oxidative damage, protect C. elegans axons from mec-4d-mediated degeneration and delay Wallerian degeneration in mice. In summary, we show that the IIS pathway is essential in maintaining neuronal homeostasis under pro-degenerative stimuli and identify ROS as a key intermediate of neuronal degeneration in vivo. Since axonal degeneration represents an early pathological event in neurodegeneration, our work identifies potential targets for therapeutic intervention in several conditions characterized by axonal loss and functional impairment.

Vyšlo v časopise: Diapause Formation and Downregulation of Insulin-Like Signaling via DAF-16/FOXO Delays Axonal Degeneration and Neuronal Loss. PLoS Genet 8(12): e32767. doi:10.1371/journal.pgen.1003141
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003141

Souhrn

Zdroje

1. ColemanMP, PerryVH (2002) Axon pathology in neurological disease: a neglected therapeutic target. Trends Neurosci 25 : 532–537.

2. SaxenaS, CaroniP (2007) Mechanisms of axon degeneration: from development to disease. Prog Neurobiol 83 : 174–191.

3. ColemanM (2005) Axon degeneration mechanisms: commonality amid diversity. Nat Rev Neurosci 6 : 889–898.

4. WangJT, MedressZA, BarresBA (2012) Axon degeneration: molecular mechanisms of a self-destruction pathway. J Cell Biol 196 : 7–18.

5. ColemanMP, FreemanMR (2010) Wallerian degeneration, wld(s), and nmnat. Annu Rev Neurosci 33 : 245–267.

6. TaoJ, RollsMM (2011) Dendrites have a rapid program of injury-induced degeneration that is molecularly distinct from developmental pruning. J Neurosci 31 : 5398–5405.

7. BarrientosSA, MartinezNW, YooS, JaraJS, ZamoranoS, et al. (2011) Axonal degeneration is mediated by the mitochondrial permeability transition pore. J Neurosci 31 : 966–978.

8. SchlaepferWW, BungeRP (1973) Effects of calcium ion concentration on the degeneration of amputated axons in tissue culture. J Cell Biol 59 : 456–470.

9. MackTG, ReinerM, BeirowskiB, MiW, EmanuelliM, et al. (2001) Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat Neurosci 4 : 1199–1206.

10. FerriA, SanesJR, ColemanMP, CunninghamJM, KatoAC (2003) Inhibiting axon degeneration and synapse loss attenuates apoptosis and disease progression in a mouse model of motoneuron disease. Curr Biol 13 : 669–673.

11. KanekoS, WangJ, KanekoM, YiuG, HurrellJM, et al. (2006) Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models. J Neurosci 26 : 9794–9804.

12. SajadiA, SchneiderBL, AebischerP (2004) Wlds-mediated protection of dopaminergic fibers in an animal model of Parkinson disease. Curr Biol 14 : 326–330.

13. HallDH, GuG, García-AñoverosJ, GongL, ChalfieM, et al. (1997) Neuropathology of degenerative cell death in Caenorhabditis elegans. J Neurosci 17 : 1033–1045.

14. XuK, TavernarakisN, DriscollM (2001) Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca(2+) release from the endoplasmic reticulum. Neuron 31 : 957–971.

15. SyntichakiP, XuK, DriscollM, TavernarakisN (2002) Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans. Nature 419 : 939–944.

16. TothML, SimonP, KovacsAL, VellaiT (2007) Influence of autophagy genes on ion-channel-dependent neuronal degeneration in Caenorhabditis elegans. J Cell Sci 120 : 1134–1141.

17. VandenabeeleP, GalluzziL, Vanden BergheT, KroemerG (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11 : 700–714.

18. FinchCE, RuvkunG (2001) The genetics of aging. Annu Rev Genomics Hum Genet 2 : 435–462.

19. ChalfieM, SulstonJ (1981) Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans. Dev Biol 82 : 358–370.

20. ChalfieM, SulstonJE, WhiteJG, SouthgateE, ThomsonJN, et al. (1985) The neural circuit for touch sensitivity in Caenorhabditis elegans. J Neurosci 5 : 956–964.

21. CassadaRC, RussellRL (1975) The dauerlarva, a post-embryonic developmental variant of the nematode Caenorhabditis elegans. Dev Biol 46 : 326–342.

22. BurnellAM, HouthoofdK, O'HanlonK, VanfleterenJR (2005) Alternate metabolism during the dauer stage of the nematode Caenorhabditis elegans. Exp Gerontol 40 : 850–856.

23. HouthoofdK, BraeckmanBP, LenaertsI, BrysK, De VreeseA, et al. (2002) Ageing is reversed, and metabolism is reset to young levels in recovering dauer larvae of C. elegans. Exp Gerontol 37 : 1015–1021.

24. LarsenPL (1993) Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci USA 90 : 8905–8909.

25. VanfleterenJR, De VreeseA (1995) The gerontogenes age-1 and daf-2 determine metabolic rate potential in aging Caenorhabditis elegans. FASEB J 9 : 1355–1361.

26. GottliebS, RuvkunG (1994) daf-2, daf-16 and daf-23: genetically interacting genes controlling Dauer formation in Caenorhabditis elegans. Genetics 137 : 107–120.

27. TulletJM, HertweckM, AnJH, BakerJ, HwangJY, et al. (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132 : 1025–1038.

28. HondaY, HondaS (1999) The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J 13 : 1385–1393.

29. McMahonM, ItohK, YamamotoM, ChanasSA, HendersonCJ, et al. (2001) The Cap'n'Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes. Cancer Res 61 : 3299–3307.

30. AnJH, BlackwellTK (2003) SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev 17 : 1882–1893.

31. ChelurDS, ErnstromGG, GoodmanMB, YaoCA, ChenL, et al. (2002) The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel. Nature 420 : 669–673.

32. ChalfieM, WolinskyE (1990) The identification and suppression of inherited neurodegeneration in Caenorhabditis elegans. Nature 345 : 410–416.

33. BrockiePJ, MadsenDM, ZhengY, MellemJ, MaricqAV (2001) Differential expression of glutamate receptor subunits in the nervous system of Caenorhabditis elegans and their regulation by the homeodomain protein UNC-42. J Neurosci 21 : 1510–1522.

34. LinK, HsinH, LibinaN, KenyonC (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28 : 139–145.

35. Arantes-OliveiraN, ApfeldJ, DillinA, KenyonC (2002) Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 295 : 502–505.

36. DurieuxJ, WolffS, DillinA (2011) The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell 144 : 79–91.

37. HsinH, KenyonC (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399 : 362–366.

38. LibinaN, BermanJR, KenyonC (2003) Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 115 : 489–502.

39. LehnerB, TischlerJ, FraserAG (2006) RNAi screens in Caenorhabditis elegans in a 96-well liquid format and their application to the systematic identification of genetic interactions. Nat Protoc 1 : 1617–1620.

40. MurphyCT, McCarrollSA, BargmannCI, FraserA, KamathRS, et al. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424 : 277–283.

41. SohalRS (2002) Role of oxidative stress and protein oxidation in the aging process. Free Radic Biol Med 33 : 37–44.

42. AdalbertR, GillingwaterTH, HaleyJE, BridgeK, BeirowskiB, et al. (2005) A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses. Eur J Neurosci 21 : 271–277.

43. HoopferED, MclaughlinT, WattsRJ, SchuldinerO, O'LearyDDM, et al. (2006) Wlds protection distinguishes axon degeneration following injury from naturally occurring developmental pruning. Neuron 50 : 883–895.

44. MacDonaldJM, BeachMG, PorpigliaE, SheehanAE, WattsRJ, et al. (2006) The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons. Neuron 50 : 869–881.

45. ZhaiRG, CaoY, HiesingerPR, ZhouY, MehtaSQ, et al. (2006) Drosophila NMNAT maintains neural integrity independent of its NAD synthesis activity. PLoS Biol 4: e416 doi:10.1371/journal.pbio.0040416.

46. FengY, YanT, ZhengJ, GeX, MuY, et al. (2010) Overexpression of Wlds or Nmnat2 in mauthner cells by single-cell electroporation delays axon degeneration in live zebrafish. J Neurosci Res 88 : 3319–3327.

47. ReedTT (2011) Lipid peroxidation and neurodegenerative disease. Free Radic Biol Med 51 : 1302–1319.

48. O'HaganR, ChalfieM, GoodmanMB (2005) The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals. Nat Neurosci 8 : 43–50.

49. HendersonST, JohnsonTE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11 : 1975–1980.

50. TatarM, BartkeA, AntebiA (2003) The endocrine regulation of aging by insulin-like signals. Science 299 : 1346–1351.

51. MattsonMP, MagnusT (2006) Ageing and neuronal vulnerability. Nat Rev Neurosci 7 : 278–294.

52. MartinB, MattsonMP, MaudsleyS (2006) Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev 5 : 332–353.

53. McCayCM, CrowellMF, MaynardLA (1989) The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935 155–171; discussion 172 p.

54. YuZF, MattsonMP (1999) Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: evidence for a preconditioning mechanism. J Neurosci Res 57 : 830–839.

55. DuanW, RangnekarVM, MattsonMP (1999) Prostate apoptosis response-4 production in synaptic compartments following apoptotic and excitotoxic insults: evidence for a pivotal role in mitochondrial dysfunction and neuronal degeneration. J Neurochem 72 : 2312–2322.

56. KregelKC, ZhangHJ (2007) An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 292: R18–36.

57. FontanaL, MeyerTE, KleinS, HolloszyJO (2004) Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A 101 : 6659–6663.

58. MeyerTE, KovacsSJ, EhsaniAA, KleinS, HolloszyJO, et al. (2006) Long-term caloric restriction ameliorates the decline in diastolic function in humans. J Am Coll Cardiol 47 : 398–402.

59. CivitareseAE, CarlingS, HeilbronnLK, HulverMH, UkropcovaB, et al. (2007) Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med 4: e76 doi:10.1371/journal.pmed.0040076.

60. SohalRS, WeindruchR (1996) Oxidative stress, caloric restriction, and aging. Science 273 : 59–63.

61. AlyKB, PipkinJL, HinsonWG, FeuersRJ, DuffyPH, et al. (1994) Chronic caloric restriction induces stress proteins in the hypothalamus of rats. Mech Ageing Dev 76 : 11–23.

62. EhrenfriedJA, EversBM, ChuKU, TownsendCMJr, ThompsonJC (1996) Caloric restriction increases the expression of heat shock protein in the gut. Ann Surg 223 : 592–597; discussion 597–599.

63. HeydariAR, YouS, TakahashiR, GutsmannA, SargeKD, et al. (1996) Effect of caloric restriction on the expression of heat shock protein 70 and the activation of heat shock transcription factor 1. Dev Genet 18 : 114–124.

64. LeeCK, KloppRG, WeindruchR, ProllaTA (1999) Gene expression profile of aging and its retardation by caloric restriction. Science 285 : 1390–1393.

65. SchulzTJ, ZarseK, VoigtA, UrbanN, BirringerM, et al. (2007) Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab 6 : 280–293.

66. VlachosM, TavernarakisN (2010) Non-apoptotic cell death in Caenorhabditis elegans. Dev Dyn 239 : 1337–1351.

67. ChungS, GumiennyTL, HengartnerMO, DriscollM (2000) A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C. elegans. Nat Cell Biol 2 : 931–937.

68. GilleyJ, ColemanMP (2010) Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons. PLoS Biol 8: e1000300 doi:10.1371/journal.pbio.1000300.

69. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77 : 71–94.

70. ChelurDS, ChalfieM (2007) Targeted cell killing by reconstituted caspases. Proc Natl Acad Sci U S A 104 : 2283–2288.

71. MelloCC, KramerJM, StinchcombD, AmbrosV (1991) Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. Embo J 10 : 3959–3970.

72. OkkemaPG, FireA (1994) The Caenorhabditis elegans NK-2 class homeoprotein CEH-22 is involved in combinatorial activation of gene expression in pharyngeal muscle. Development 120 : 2175–2186.

73. GoldenJW, RiddleDL (1984) The Caenorhabditis elegans dauer larva: developmental effects of pheromone, food, and temperature. Dev Biol 102 : 368–378.

74. FraserAG, KamathRS, ZipperlenP, Martinez-CamposM, SohrmannM, et al. (2000) Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408 : 325–330.

75. KamathRS, FraserAG, DongY, PoulinG, DurbinR, et al. (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421 : 231–237.

76. Reagan-ShawS, NihalM, AhmadN (2008) Dose translation from animal to human studies revisited. FASEB J 22 : 659–661.

77. ContrerasL, MellaD, MoenneA, CorreaJA (2009) Differential responses to copper-induced oxidative stress in the marine macroalgae Lessonia nigrescens and Scytosiphon lomentaria (Phaeophyceae). Aquat Toxicol 94 : 94–102.