Reduced activity of AMP-activated protein kinase protects against genetic models of motor neuron disease

Journal of Neuroscience

Volumn 32, Issue 3, 2012, Pages 1123-1141

  Lim, M A ^a,b   Selak, M A ^c   Xiang, Z ^d   Krainc, D ^d   Neve, R L ^e   Kraemer, B C ^f   Watts, J L ^g   Kalb, R G ^a,b  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c Uniformed Services University of the Health Sciences   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

^e MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^f VA PUGET SOUND HEALTH CARE SYSTEM   (United States)

^g WASHINGTON STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COPPER ZINC SUPEROXIDE DISMUTASE; DNA BINDING PROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOLOGICAL MODEL; CAENORHABDITIS ELEGANS; CELL ENERGY; CONTROLLED STUDY; DEATH; ENERGY EXPENDITURE; FEMALE; FERTILITY; GENE; GENE SILENCING; HUMAN; HUMAN CELL; IMMUNOBLOTTING; LOCOMOTION; MALE; MOTOR NEURON DISEASE; MOUSE; MUTANT; NEMATODE; NEWBORN; NONHUMAN; OXYGEN CONSUMPTION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SPINAL CORD; TBC1D1 GENE; WESTERN BLOTTIING; WILD TYPE; WORM;

ADENOSINE TRIPHOSPHATE; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; ANIMALS, GENETICALLY MODIFIED; ANIMALS, NEWBORN; CAENORHABDITIS ELEGANS; CAENORHABDITIS ELEGANS PROTEINS; DISEASE MODELS, ANIMAL; DNA-BINDING PROTEINS; ENZYME INHIBITORS; FERTILITY; GENE EXPRESSION REGULATION; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LOCOMOTION; MALE; MICE; MICE, INBRED C57BL; MOTOR NEURON DISEASE; MOTOR NEURONS; MUTATION; OXYGEN CONSUMPTION; PROTEIN SUBUNITS; PROTEIN-SERINE-THREONINE KINASES; RATS; RATS, SPRAGUE-DAWLEY; RNA INTERFERENCE; SPINAL CORD; SUPEROXIDE DISMUTASE; TRANS-ACTIVATORS; TRANSFECTION;

EID: 84855993170     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.6554-10.2012     Document Type: Article

References (97)

1. Barnes JA, Ebner BA, Duvick LA, Gao W, Chen G, Orr HT, Ebner TJ (2011) Abnormalities in the climbing fiber-Purkinje cell circuitry contribute to neuronal dysfunction in ATXN1[82Q] mice. J Neurosci 31:12778-12789.
2. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG (2006) Resveratrol improves health and survival of mice on a highcalorie diet. Nature 444:337-342.
3. Bendotti C, Calvaresi N, Chiveri L, Prelle A, Moggio M, Braga M, Silani V, De Biasi S (2001) Early vacuolization and mitochondrial damage in motor neurons of FALS mice are not associated with apoptosis or with changes in cytochrome oxidase histochemical reactivity. J Neurol Sci 191:25-33.
4. Bouteloup C, Desport JC, Clavelou P, Guy N, Derumeaux-Burel H, Ferrier A, Couratier P (2009) Hypermetabolism in ALS patients: an early and persistent phenomenon. J Neurol 256:1236-1242.
5. Branicky R, Benard C, Hekimi S (2000) Clk-1, mitochondria, and physiological rates. Bioessays 22:48-56.
6. Braun RJ, Sommer C, Carmona-Gutierrez D, Khoury CM, Ring J, Buttner S, Madeo F (2011) Neurotoxic 43-kDa TAR DNA-binding protein (TDP- 43) triggers mitochondrion-dependent programmed cell death in yeast. J Biol Chem 286:19958-19972.
7. Browne SE, Yang L, DiMauro JP, Fuller SW, Licata SC, Beal MF (2006) Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALS. Neurobiol Dis 22:599-610.
8. Calixto A, Chelur D, Topalidou I, Chen X, Chalfie M (2010) Enhanced neuronal RNAi in C. elegans using SID-1. Nat Methods 7:554-559.
9. Cardozo E, Pavone ME, Hirshfeld-Cytron JE (2011) Metabolic syndrome and oocyte quality. Trends Endocrinol Metab 22:103-109.
10. Cassina P, Cassina A, Pehar M, Castellanos R, Gandelman M, de Leon A, Robinson KM, Mason RP, Beckman JS, Barbeito L, Radi R (2008) Mitochondrial dysfunction in SOD1G93A-bearing astrocytes promotes motor neuron degeneration: Prevention by mitochondrial-targeted antioxidants. J Neurosci 28:4115-4122.
11. Chadt A, Leicht K, Deshmukh A, Jiang LQ, Scherneck S, Bernhardt U, Dreja T, Vogel H, Schmolz K, Kluge R, Zierath JR, Hultschig C, Hoeben RC, Schurmann A, Joost HG, Al-Hasani H (2008) Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity. Nat Genet 40:1354-1359.
12. Chaturvedi RK, Adhihetty P, Shukla S, Hennessy T, Calingasan N, Yang L, Starkov A, Kiaei M, Cannella M, Sassone J, Ciammola A, Squitieri F, Beal MF (2009) Impaired PGC-1alpha function in muscle in Huntington's disease. Hum Mol Genet 18:3048-3065.
13. Chavez JA, Roach WG, Keller SR, Lane WS, Lienhard GE (2008) Inhibition of GLUT4 translocation by Tbc1d1, a rab GTPase-activating protein abundant in skeletal muscle, is partially relieved by AMP-activated protein kinase activation. J Biol Chem 283:9187-9195.
14. Chehab FF, Lim ME, Lu R (1996) Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 12:318-320.
15. Chen Y, Zhou K, Wang R, Liu Y, Kwak YD, Ma T, Thompson RC, Zhao Y, Smith L, Gasparini L, Luo Z, Xu H, Liao FF (2009) Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Proc Natl Acad SciU S A 106:3907-3912.
16. Chiang PM, Ling J, Jeong YH, Price DL, Aja SM, Wong PC (2010) Deletion of TDP-43 down-regulates Tbc1d1, a gene linked to obesity, and alters body fat metabolism. Proc Natl Acad Sci U S A 107:16320-16324.
17. Cinar H, Keles S, Jin Y (2005) Expression profiling of GABAergic motor neurons in Caenorhabditis elegans. Curr Biol 15:340-346.
18. Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D (2006) Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127:59-69.
19. Curtis R, O'Connor G, DiStefano PS (2006) Aging networks in Caenorhabditis elegans: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways. Aging Cell 5:119-126.
20. Deng HX, Shi Y, Furukawa Y, Zhai H, Fu R, Liu E, Gorrie GH, Khan MS, Hung WY, Bigio EH, Lukas T, Dal Canto MC, O'Halloran TV, Siddique T (2006) Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria. Proc Natl Acad Sci U S A 103:7142-7147.
21. Desport JC, Preux PM, Magy L, Boirie Y, Vallat JM, Beaufrere B, Couratier P (2001) Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. Am J Clin Nutr 74:328-334.
22. Desport JC, Torny F, Lacoste M, Preux PM, Couratier P (2005) Hypermetabolism in ALS: Correlations with clinical and paraclinical parameters. Neurodegener Dis 2:202-207.
23. Donato J Jr, Cravo RM, Frazao R, Elias CF (2011) Hypothalamic sites of leptin action linking metabolism and reproduction. Neuroendocrinology 93:9-18.
24. Dupuis L, Oudart H, Rene F, Gonzalez de Aguilar JL, Loeffler JP (2004) Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: Benefit of a high-energy diet in a transgenic mouse model. Proc Natl Acad Sci U S A 101:11159-11164.
25. Dupuis L, Corcia P, Fergani A, Gonzalez De Aguilar JL, Bonnefont-Rousselot D, Bittar R, Seilhean D, Hauw JJ, Lacomblez L, Loeffler JP, Meininger V (2008) Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology 70:1004-1009.
26. Dupuis L, Pradat PF, Ludolph AC, Loeffler JP (2011) Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 10:75-82.
27. Feinberg EH, Hunter CP (2003) Transport of dsRNA into cells by the transmembrane protein SID-1. Science 301:1545-1547.
28. Fergani A, Oudart H, Gonzalez De Aguilar JL, Fricker B, Rene F, Hocquette JF, Meininger V, Dupuis L, Loeffler JP (2007) Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosis. J Lipid Res 48:1571-1580.
29. Ferri A, Cozzolino M, Crosio C, Nencini M, Casciati A, Gralla EB, Rotilio G, Valentine JS, Carri MT (2006) Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials. Proc Natl Acad Sci U S A 103:13860-13865.
30. Finck BN, Kelly DP (2006) PGC-1 coactivators: Inducible regulators of energy metabolism in health and disease. J Clin Invest 116:615-622.
31. Fraser AG, Kamath RS, Zipperlen P, Martinez-Campos M, Sohrmann M, Ahringer J (2000) Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408:325-330.
32. Frosig C, Pehmoller C, Birk JB, Richter EA, Wojtaszewski JF (2010) Exercise-induced TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle. J Physiol 588:4539-4548.
33. Funalot B, Desport JC, Sturtz F, Camu W, Couratier P (2009) High metabolic level in patients with familial amyotrophic lateral sclerosis. Amyotroph Lateral Scler 10:113-117.
34. Gidalevitz T, Krupinski T, Garcia S, Morimoto RI (2009) Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity. PLoS Genet 5:e1000399.
35. Gonzalez de Aguilar JL, Gordon JW, Rene F, de Tapia M, Lutz-Bucher B, Gaiddon C, Loeffler JP (2000) Alteration of the bcl-x/Bax ratio in a transgenic mouse model of amyotrophic lateral sclerosis: evidence for the implication of the p53 signaling pathway. Neurobiol Dis 7:406-415.
36. Gonzalez de Aguilar JL, Niederhauser-Wiederkehr C, Halter B, De Tapia M, Di Scala F, Demougin P, Dupuis L, Primig M, Meininger V, Loeffler JP (2008) Gene profiling of skeletal muscle in an amyotrophic lateral sclerosis mouse model. Physiol Genomics 32:207-218.
37. Gould TW, Buss RR, Vinsant S, Prevette D, Sun W, Knudson CM, Milligan CE, Oppenheim RW (2006) Complete dissociation of motor neuron death from motor dysfunction by bax deletion in a mouse model of ALS. J Neurosci 26:8774-8786.
38. Hamadeh MJ, Rodriguez MC, Kaczor JJ, Tarnopolsky MA (2005) Caloric restriction transiently improves motor performance but hastens clinical onset of disease in the Cu/Zn-superoxide dismutase mutant G93A mouse. Muscle Nerve 31:214-220.
39. Han SM, Cottee PA, Miller MA (2010) Sperm and oocyte communication mechanisms controlling C. elegans fertility. Dev Dyn 239:1265-1281.
40. Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774-785.
41. Hathorn T, Snyder-Keller A, Messer A (2011) Nicotinamide improves motor deficits and upregulates PGC-1alpha and BDNF gene expression in a mouse model of Huntington's disease. Neurobiol Dis 41:43-50.
42. Hsin H, Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399:362-366.
43. Ilieva HS, Yamanaka K, Malkmus S, Kakinohana O, Yaksh T, Marsala M, Cleveland DW (2008) Mutant dynein (loa) triggers proprioceptive axon loss that extends survival only in the SOD1 ALS model with highest motor neuron death. Proc Natl Acad Sci U S A 105:12599-12604.
44. Irrcher I, Ljubicic V, Kirwan AF, Hood DA (2008) AMP-activated protein kinase-regulated activation of the PGC-1alpha promoter in skeletal muscle cells. PLoS One 3:e3614.
45. Israelson A, Arbel N, Da Cruz S, Ilieva H, Yamanaka K, Shoshan-Barmatz V, Cleveland DW (2010) Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of inherited ALS. Neuron 67:575-587.
46. Jager S, Handschin C, St-Pierre J, Spiegelman BM (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A 104:12017-12022.
47. Jekabsons MB, Nicholls DG (2004) In situ respiration and bioenergetic status of mitochondria in primary cerebellar granule neuronal cultures exposed continuously to glutamate. J Biol Chem 279:32989-33000.
48. Jeong GB, Werner M, Gazula VR, Itoh T, Roberts M, David S, Pfister B, Cohen A, Neve RL, Hollmann M, Kalb R (2006) Bi-directional control of motor neuron dendrite remodeling by the calcium permeability of AMPA receptors. Mol Cell Neurosci 32:299-314.
49. Johnson WG, Lucek PR, Chatkupt S, Furman Y, Lustenberger A, Lazzarini A (1995) Reduced fecundity in male ALS gene-carriers. Am J Med Genet 59:149-153.
50. Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ, Thompson CB (2005) AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 18:283-293.
51. Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1:15-25.
52. Kasarskis EJ, Berryman S, Vanderleest JG, Schneider AR, McClain CJ (1996) Nutritional status of patients with amyotrophic lateral sclerosis: Relation to the proximity of death. Am J Clin Nutr 63:130-137.
53. Kim SM, Kim H, Kim JE, Park KS, Sung JJ, Kim SH, Lee KW (2011) Amyotrophic lateral sclerosis is associated with hypolipidemia at the presymptomatic stage in mice. PLoS One 6:e17985.
54. Kubagawa HM, Watts JL, Corrigan C, Edmonds JW, Sztul E, Browse J, Miller MA (2006) Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment in vivo. Nat Cell Biol 8:1143-1148.
55. Lee H, Cho JS, Lambacher N, Lee J, Lee SJ, Lee TH, Gartner A, Koo HS (2008) The Caenorhabditis elegans AMP-activated protein kinase AAK-2 is phosphorylated by LKB1 and is required for resistance to oxidative stress and for normal motility and foraging behavior. J Biol Chem 283:14988-14993.
56. Li J, Zeng Z, Viollet B, Ronnett GV, McCullough LD (2007) Neuroprotective effects of adenosine monophosphate-activated protein kinase inhibition and gene deletion in stroke. Stroke 38:2992-2999.
57. Liachko NF, Guthrie CR, Kraemer BC (2010) Phosphorylation promotes neurotoxicity in a Caenorhabditis elegans model of TDP-43 proteinopathy. J Neurosci 30:16208-16219.
58. Lobsiger CS, Boillee S, Cleveland DW (2007) Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons. Proc Natl Acad Sci U S A 104:7319-7326.
59. Long YC, Zierath JR (2006) AMP-activated protein kinase signaling in metabolic regulation. J Clin Invest 116:1776-1783.
60. Lu JY, Lin YY, Sheu JC, Wu JT, Lee FJ, Chen Y, Lin MI, Chiang FT, Tai TY, Berger SL, Zhao Y, Tsai KS, Zhu H, Chuang LM, Boeke JD (2011) Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction. Cell 146:969-979.
61. Lukas TJ, Luo WW, Mao H, Cole N, Siddique T (2006) Informatics-assisted protein profiling in a transgenic mouse model of amyotrophic lateral sclerosis. Mol Cell Proteomics 5:1233-1244.
62. Luo S, Kleemann GA, Ashraf JM, Shaw WM, Murphy CT (2010) TGF-beta and insulin signaling regulate reproductive aging via oocyte and germline quality maintenance. Cell 143:299-312.
63. Martin LJ (2000) p53 is abnormally elevated and active in the CNS of patients with amyotrophic lateral sclerosis. Neurobiol Dis 7:613-622.
64. Martinez JA, Francis GJ, Liu WQ, Pradzinsky N, Fine J, Wilson M, Hanson LR, Frey WH II, Zochodne D, Gordon T, Toth C (2008) Intranasal delivery of insulin and a nitric oxide synthase inhibitor in an experimental model of amyotrophic lateral sclerosis. Neuroscience 157:908-925.
65. Mattiazzi M, D'Aurelio M, Gajewski CD, Martushova K, Kiaei M, Beal MF, Manfredi G (2002) Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice. J Biol Chem 277:29626-29633.
66. Mattson MP, Cutler RG, Camandola S (2007) Energy intake and amyotrophic lateral sclerosis. Neuromolecular Med 9:17-20.
67. McConoughey SJ, Basso M, Niatsetskaya ZV, Sleiman SF, Smirnova NA, Langley BC, Mahishi L, Cooper AJ, Antonyak MA, Cerione RA, Li B, Starkov A, Chaturvedi RK, Beal MF, Coppola G, Geschwind DH, Ryu H, Xia L, Iismaa SE, Pallos J, et al. (2010) Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington disease. EMBO Mol Med 2:349-370.
68. McCullough LD, Zeng Z, Li H, Landree LE, McFadden J, Ronnett GV (2005) Pharmacological inhibition of AMP-activated protein kinase provides neuroprotection in stroke. J Biol Chem 280:20493-20502.
69. Mentis GZ, Blivis D, Liu W, Drobac E, Crowder ME, Kong L, Alvarez FJ, Sumner CJ, O'Donovan MJ (2011) Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy. Neuron 69:453-467.
70. Mojsilovic-Petrovic J, Jeong GB, Crocker A, Arneja A, David S, Russell DS, Kalb RG (2006) Protecting motor neurons from toxic insult by antagonism of adenosine A2a and trk receptors. J Neurosci 26:9250-9263.
71. Mojsilovic-Petrovic J, Nedelsky N, Boccitto M, Mano I, Georgiades SN, Zhou W, Liu Y, Neve RL, Taylor JP, Driscoll M, Clardy J, Merry D, Kalb RG (2009) FOXO3a is broadly neuroprotective in vitro and in vivo against insults implicated in motor neuron diseases. J Neurosci 29:8236-8247.
72. Morimoto N, Nagai M, Ohta Y, Miyazaki K, Kurata T, Morimoto M, Murakami T, Takehisa Y, Ikeda Y, Kamiya T, Abe K (2007) Increased autophagy in transgenic mice with a G93A mutant SOD1 gene. Brain Res 1167:112-117.
73. Mu J, Brozinick JT Jr, Valladares O, Bucan M, Birnbaum MJ (2001) A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell 7:1085-1094.
74. Mukherjee P, Mulrooney TJ, Marsh J, Blair D, Chiles TC, Seyfried TN (2008) Differential effects of energy stress on AMPK phosphorylation and apoptosis in experimental brain tumor and normal brain. Mol Cancer 7:37-52.
75. Neve RL, Howe JR, Hong S, Kalb RG (1997) Introduction of the glutamate receptor subunit 1 into motor neurons in vitro and in vivo using a recombinant herpes simplex virus. Neuroscience 79:435-447.
76. Okoshi R, Ozaki T, Yamamoto H, Ando K, Koida N, Ono S, Koda T, Kamijo T, Nakagawara A, Kizaki H (2008) Activation of AMP-activated protein kinase induces p53-dependent apoptotic cell death in response to energetic stress. J Biol Chem 283:3979-3987.
77. Onken B, Driscoll M (2010) Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans healthspan via AMPK, LKB1, and SKN-1. PLoS One 5:e8758.
78. Patel BP, Safdar A, Raha S, Tarnopolsky MA, Hamadeh MJ (2010) Caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the G93A mouse, an animal model of ALS. PLoS One 5:e9386.
79. Pedrini S, Sau D, Guareschi S, Bogush M, Brown RH Jr, Naniche N, Kia A, Trotti D, Pasinelli P (2010) ALS-linked mutant SOD1 damages mitochondria by promoting conformational changes in bcl-2. Hum Mol Genet 19:2974-2986.
80. Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): Transcriptional coactivator and metabolic regulator. Endocr Rev 24:78-90.
81. Rothstein JD (2009) Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol 65 [Suppl 1]:S3-S9.
82. Shakkottai VG, do Carmo Costa M, Dell'Orco JM, Sankaranarayanan A, Wulff H, Paulson HL (2011) Early changes in cerebellar physiology accompany motor dysfunction in the polyglutamine disease spinocerebellar ataxia type 3. J Neurosci 31:13002-13014.
83. Shan X, Chiang PM, Price DL, Wong PC (2010) Altered distributions of gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice. Proc Natl Acad Sci U S A 107:16325-16330.
84. Shih JD, Hunter CP (2011) SID-1 is a dsRNA-selective dsRNA-gated channel. RNA 17:1057-1065.
85. Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, Troconso JC, Dawson VL, Dawson TM (2011) PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease. Cell 144:689-702.
86. Soukas AA, Kane EA, Carr CE, Melo JA, Ruvkun G (2009) Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans. Genes Dev 23:496-511.
87. Spampanato J, Gu X, Yang XW, Mody I (2008) Progressive synaptic pathology of motor cortical neurons in a BAC transgenic mouse model of Huntington's disease. Neuroscience 157:606-620.
88. Timmons L, Fire A (1998) Specific interference by ingested dsRNA. Nature 395:854.
89. Turnley AM, Stapleton D, Mann RJ, Witters LA, Kemp BE, Bartlett PF (1999) Cellular distribution and developmental expression of AMPactivated protein kinase isoforms in mouse central nervous system. J Neurochem 72:1707-1716.
90. Viollet B, Andreelli F, Jorgensen SB, Perrin C, Geloen A, Flamez D, Mu J, Lenzner C, Baud O, Bennoun M, Gomas E, Nicolas G, Wojtaszewski JF, Kahn A, Carling D, Schuit FC, Birnbaum MJ, Richter EA, Burcelin R, Vaulont S (2003) The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity. J Clin Invest 111:91-98.
91. Wang J, Farr GW, Hall DH, Li F, Furtak K, Dreier L, Horwich AL (2009) An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans. PLoS Genet 5:e1000350.
92. Weydt P, Pineda VV, Torrence AE, Libby RT, Satterfield TF, Lazarowski ER, Gilbert ML, Morton GJ, Bammler TK, Strand AD, Cui L, Beyer RP, Easley CN, Smith AC, Krainc D, Luquet S, Sweet IR, Schwartz MW, La Spada AR (2006) Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab 4:349-362.
93. Weydt P, Soyal SM, Gellera C, Didonato S, Weidinger C, Oberkofler H, Landwehrmeyer GB, Patsch W (2009) The gene coding for PGC-1alpha modifies age at onset in Huntington's disease. Mol Neurodegener 4:3-9.
94. Winston WM, Molodowitch C, Hunter CP (2002) Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science 295:2456-2459.
95. Xu YF, Gendron TF, Zhang YJ, Lin WL, D'Alton S, Sheng H, Casey MC, Tong J, Knight J, Yu X, Rademakers R, Boylan K, Hutton M, McGowan E, Dickson DW, Lewis J, Petrucelli L (2010) Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice. J Neurosci 30:10851-10859.
96. Zhao Z, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J, Humala N, Thiyagarajan M, Wang J, Pasinetti GM (2006) A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci 7:29-39.
97. Zhou J, Yi J, Fu R, Liu E, Siddique T, Rios E, Deng HX (2010) Hyperactive intracellular calcium signaling associated with localized mitochondrial defects in skeletal muscle of an animal model of amyotrophic lateral sclerosis. J Biol Chem 285:705-712.