Protein recycling pathways in neurodegenerative diseases

Alzheimer's Research and Therapy

Volumn 6, Issue 2, 2014, Pages

  Fecto, Faisal ^a   Esengul, Y Taylan ^a   Siddique, Teepu ^a,b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; AUTOPHAGY; DEGENERATIVE DISEASE; FRONTOTEMPORAL DEMENTIA; HUMAN; HUNTINGTON CHOREA; NERVE CELL; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN QUALITY; REVIEW; SIGNAL TRANSDUCTION;

EID: 84896776302     PISSN: None     EISSN: 17589193     Source Type: Journal    
DOI: 10.1186/alzrt243     Document Type: Review

References (131)

1. Protein quality control in neurodegenerative disease. JE Gestwicki, D Garza, Prog Mol Biol Transl Sci 2012 107 327 353 22482455
2. The role of the ubiquitin proteasome system in synapse remodeling and neurodegenerative diseases. M Ding, K Shen, Bioessays 2008 30 1075 1083 10.1002/bies.20843 18937340
3. Autophagosomes in GFP-LC3 transgenic mice. N Mizushima, A Kuma, Methods Mol Biol 2008 445 119 124 10.1007/978-1-59745-157-4-7 18425446
4. Protein turnover differences between neurons and other cells. AS Tsvetkov, S Mitra, S Finkbeiner, Autophagy 2009 5 1037 1038 10.4161/auto.5.7. 9291 19838079
5. The ubiquitin-proteasome pathway and synaptic plasticity. AN Hegde, Learn Mem 2010 17 314 327 10.1101/lm.1504010 20566674
6. Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction. HC Tai, EM Schuman, Nat Rev Neurosci 2008 9 826 838 10.1038/nrn2499 18931696
7. The ubiquitin proteasome system in neurodegenerative diseases: culprit, accomplice or victim? FJ Dennissen, N Kholod, FW van Leeuwen, Prog Neurobiol 2012 96 190 207 10.1016/j.pneurobio.2012.01.003 22270043
8. Neuronal autophagy and neurodegenerative diseases. JH Son, JH Shim, KH Kim, JY Ha, JY Han, Exp Mol Med 2012 44 89 98 10.3858/emm.2012.44.2.031 22257884
9. Biological and chemical approaches to diseases of proteostasis deficiency. ET Powers, RI Morimoto, A Dillin, JW Kelly, WE Balch, Annu Rev Biochem 2009 78 959 991 10.1146/annurev.biochem.052308.114844 19298183
10. Metastability of native proteins and the phenomenon of amyloid formation. AJ Baldwin, TP Knowles, GG Tartaglia, AW Fitzpatrick, GL Devlin, SL Shammas, CA Waudby, MF Mossuto, S Meehan, SL Gras, J Christodoulou, SJ Anthony-Cahill, PD Barker, M Vendruscolo, CM Dobson, J Am Chem Soc 2011 133 14160 14163 10.1021/ja2017703 21650202
11. Autophagy and aging: the importance of maintaining "clean" cells. AM Cuervo, E Bergamini, UT Brunk, W Droge, M Ffrench, A Terman, Autophagy 2005 1 131 140 10.4161/auto.1.3.2017 16874025
12. The cerebral proteopathies: neurodegenerative disorders of protein conformation and assembly. LC Walker, H LeVine, Mol Neurobiol 2000 21 83 95 10.1385/MN:21:1-2:083 11327151
13. Progressive disruption of cellular protein folding in models of polyglutamine diseases. T Gidalevitz, A Ben-Zvi, KH Ho, HR Brignull, RI Morimoto, Science 2006 311 1471 1474 10.1126/science.1124514 16469881
14. Protein homeostasis and aging in neurodegeneration. PM Douglas, A Dillin, J Cell Biol 2010 190 719 729 10.1083/jcb.201005144 20819932
15. Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. RI Morimoto, Genes Dev 2008 22 1427 1438 10.1101/gad.1657108 18519635
16. Molecular chaperones antagonize proteotoxicity by differentially modulating protein aggregation pathways. PM Douglas, DW Summers, DM Cyr, Prion 2009 3 51 58 10.4161/pri.3.2.8587 19421006
17. Integration of clearance mechanisms: the proteasome and autophagy. E Wong, AM Cuervo, Cold Spring Harb Perspect Biol 2010 2 006734 21068151
18. Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies. L Bedford, D Hay, A Devoy, S Paine, DG Powe, R Seth, T Gray, I Topham, K Fone, N Rezvani, M Mee, T Soane, R Layfield, PW Sheppard, T Ebendal, D Usoskin, J Lowe, RJ Mayer, J Neurosci 2008 28 8189 8198 10.1523/JNEUROSCI.2218-08.2008 18701681
19. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. T Hara, K Nakamura, M Matsui, A Yamamoto, Y Nakahara, R Suzuki-Migishima, M Yokoyama, K Mishima, I Saito, H Okano, N Mizushima, Nature 2006 441 885 889 10.1038/nature04724 16625204
20. Loss of autophagy in the central nervous system causes neurodegeneration in mice. M Komatsu, S Waguri, T Chiba, S Murata, J Iwata, I Tanida, T Ueno, M Koike, Y Uchiyama, E Kominami, K Tanaka, Nature 2006 441 880 884 10.1038/nature04723 16625205
21. Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection. NB Nedelsky, PK Todd, JP Taylor, Biochim Biophys Acta 2008 1782 691 699 10.1016/j.bbadis.2008.10.002 18930136
22. Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. VI Korolchuk, A Mansilla, FM Menzies, DC Rubinsztein, Mol Cell 2009 33 517 527 10.1016/j.molcel.2009.01.021 19250912
23. UBQLN2/P62 cellular recycling pathways in amyotrophic lateral sclerosis and frontotemporal dementia. F Fecto, T Siddique, Muscle Nerve 2012 45 157 162 10.1002/mus.23278 22246868
24. Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration. H Koga, AM Cuervo, Neurobiol Dis 2011 43 29 37 10.1016/j.nbd.2010.07.006 20643207
25. Tau protein degradation is catalyzed by the ATP/ubiquitin-independent 20S proteasome under normal cell conditions. T Grune, D Botzen, M Engels, P Voss, B Kaiser, T Jung, S Grimm, G Ermak, KJ Davies, Arch Biochem Biophys 2010 500 181 188 10.1016/j.abb.2010.05.008 20478262
26. Proteasome inhibition by paired helical filament-tau in brains of patients with Alzheimer's disease. S Keck, R Nitsch, T Grune, O Ullrich, J Neurochem 2003 85 115 122 10.1046/j.1471-4159.2003.01642.x 12641733
27. Abeta inhibits the proteasome and enhances amyloid and tau accumulation. BP Tseng, KN Green, JL Chan, M Blurton-Jones, FM LaFerla, Neurobiol Aging 2008 29 1607 1618 10.1016/j.neurobiolaging.2007.04.014 17544172
28. Impaired proteasome function in Alzheimer's disease. JN Keller, KB Hanni, WR Markesbery, J Neurochem 2000 75 436 439 10854289
29. Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients. FW van Leeuwen, DP de Kleijn, HH van den Hurk, A Neubauer, MA Sonnemans, JA Sluijs, S Köycü RD Ramdjielal, A Salehi, GJ Martens, FG Grosveld, J Peter, H Burbach, EM Hol, Science 1998 279 242 247 10.1126/science.279.5348.242 9422699
30. Misframed proteins and neurodegeneration: a novel view on Alzheimer's and Parkinson's diseases. FJ Dennissen, N Kholod, HW Steinbusch, FW Van Leeuwen, Neurodegener Dis 2010 7 76 79 10.1159/000285510 20173331
31. Dose-dependent inhibition of proteasome activity by a mutant ubiquitin associated with neurodegenerative disease. P van Tijn, FM de Vrij, KG Schuurman, NP Dantuma, DF Fischer, FW van Leeuwen, EM Hol, J Cell Sci 2007 120 1615 1623 10.1242/jcs.03438 17405812
32. Structural basis of E2-25 K/UBB + 1 interaction leading to proteasome inhibition and neurotoxicity. S Ko, GB Kang, SM Song, JG Lee, DY Shin, JH Yun, Y Sheng, C Cheong, YH Jeon, YK Jung, CH Arrowsmith, GV Avvakumov, S Dhe-Paganon, YJ Yoo, SH Eom, W Lee, J Biol Chem 2010 285 36070 36080 10.1074/jbc.M110.145219 20826778
33. Emerging role of Alzheimer's disease-associated ubiquilin-1 in protein aggregation. A Haapasalo, J Viswanathan, L Bertram, H Soininen, RE Tanzi, M Hiltunen, Biochem Soc Trans 2010 38 150 155 10.1042/BST0380150 20074050
34. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. RA Nixon, J Wegiel, A Kumar, WH Yu, C Peterhoff, A Cataldo, AM Cuervo, J Neuropathol Exp Neurol 2005 64 113 122 15751225
35. Macroautophagy-a novel beta-amyloid peptide-generating pathway activated in Alzheimer's disease. WH Yu, AM Cuervo, A Kumar, CM Peterhoff, SD Schmidt, JH Lee, PS Mohan, M Mercken, MR Farmery, LO Tjernberg, Y Jiang, K Duff, Y Uchiyama, J Näslund, PM Mathews, AM Cataldo, RA Nixon, J Cell Biol 2005 171 87 98 10.1083/jcb.200505082 16203860
36. Autophagy, amyloidogenesis and Alzheimer disease. RA Nixon, J Cell Sci 2007 120 4081 4091 10.1242/jcs.019265 18032783
37. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease. B Boland, A Kumar, S Lee, FM Platt, J Wegiel, WH Yu, RA Nixon, J Neurosci 2008 28 6926 6937 10.1523/JNEUROSCI.0800-08.2008 18596167
38. Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. A Caccamo, S Majumder, A Richardson, R Strong, S Oddo, J Biol Chem 2010 285 13107 13120 10.1074/jbc.M110.100420 20178983
39. Naturally secreted amyloid-beta increases mammalian target of rapamycin (mTOR) activity via a PRAS40-mediated mechanism. A Caccamo, MA Maldonado, S Majumder, DX Medina, W Holbein, A Magri, S Oddo, J Biol Chem 2011 286 8924 8932 10.1074/jbc.M110.180638 21266573
40. Coupling of mammalian target of rapamycin with phosphoinositide 3-kinase signaling pathway regulates protein phosphatase 2A- and glycogen synthase kinase-3 -dependent phosphorylation of Tau. V Meske, F Albert, TG Ohm, J Biol Chem 2008 283 100 109 10.1074/jbc.M704292200 17971449
41. Autophagy protects neuron from Abeta-induced cytotoxicity. SY Hung, WP Huang, HC Liou, WM Fu, Autophagy 2009 5 502 510 10.4161/auto.5.4.8096 19270530
42. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. JH Lee, WH Yu, A Kumar, S Lee, PS Mohan, CM Peterhoff, DM Wolfe, M Martinez-Vicente, AC Massey, G Sovak, Y Uchiyama, D Westaway, AM Cuervo, RA Nixon, Cell 2010 141 1146 1158 10.1016/j.cell.2010.05.008 20541250
43. Inhibition of glycogen synthase kinase-3 ameliorates beta-amyloid pathology and restores lysosomal acidification and mammalian target of rapamycin activity in the Alzheimer disease mouse model: in vivo and in vitro studies. L Avrahami, D Farfara, M Shaham-Kol, R Vassar, D Frenkel, H Eldar-Finkelman, J Biol Chem 2013 288 1295 1306 10.1074/jbc.M112.409250 23155049
44. Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification. DM Wolfe, JH Lee, A Kumar, S Lee, SJ Orenstein, RA Nixon, Eur J Neurosci 2013 37 1949 1961 10.1111/ejn.12169 23773064
45. Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus. M Torres, S Jimenez, R Sanchez-Varo, V Navarro, L Trujillo-Estrada, E Sanchez-Mejias, I Carmona, JC Davila, M Vizuete, A Gutierrez, J Vitorica, Mol Neurodegener 2012 7 59 10.1186/1750-1326-7-59 23173743
46. Presenilin deficiency or lysosomal inhibition enhances Wnt signaling through relocalization of GSK3 to the late-endosomal compartment. R Dobrowolski, P Vick, D Ploper, I Gumper, H Snitkin, DD Sabatini, EM De Robertis, Cell Rep 2012 2 1316 1328 10.1016/j.celrep.2012.09.026 23122960
47. A role for presenilins in autophagy revisited: normal acidification of lysosomes in cells lacking PSEN1 and PSEN2. X Zhang, K Garbett, K Veeraraghavalu, B Wilburn, R Gilmore, K Mirnics, SS Sisodia, J Neurosci 2012 32 8633 8648 10.1523/JNEUROSCI.0556-12.2012 22723704
48. Lysosomal calcium homeostasis defects, not proton pump defects, cause endo-lysosomal dysfunction in PSEN-deficient cells. K Coen, RS Flannagan, S Baron, LR Carraro-Lacroix, D Wang, W Vermeire, C Michiels, S Munck, V Baert, S Sugita, F Wuytack, PR Hiesinger, S Grinstein, W Annaert, J Cell Biol 2012 198 23 35 10.1083/jcb.201201076 22753898
49. Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits. DS Yang, P Stavrides, PS Mohan, S Kaushik, A Kumar, M Ohno, SD Schmidt, D Wesson, U Bandyopadhyay, Y Jiang, M Pawlik, CM Peterhoff, AJ Yang, DA Wilson, P St George-Hyslop, D Westaway, PM Mathews, E Levy, AM Cuervo, RA Nixon, Brain 2011 134 258 277 10.1093/brain/awq341 21186265
50. Fighting neurodegeneration with rapamycin: mechanistic insights. J Bove, M Martinez-Vicente, M Vila, Nat Rev Neurosci 2011 12 437 452 10.1038/nrn3068 21772323
51. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. P Spilman, N Podlutskaya, MJ Hart, J Debnath, O Gorostiza, D Bredesen, A Richardson, R Strong, V Galvan, PLoS One 2010 5 9979 10.1371/journal.pone.0009979 20376313
52. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. F Pickford, E Masliah, M Britschgi, K Lucin, R Narasimhan, PA Jaeger, S Small, B Spencer, E Rockenstein, B Levine, T Wyss-Coray, J Clin Invest 2008 118 2190 2199 18497889
53. A transient, neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis. A Casadio, KC Martin, M Giustetto, H Zhu, M Chen, D Bartsch, CH Bailey, ER Kandel, Cell 1999 99 221 237 10.1016/S0092-8674(00)81653-0 10535740
54. Rapamycin-sensitive signalling in long-term consolidation of auditory cortex-dependent memory. W Tischmeyer, H Schicknick, M Kraus, CI Seidenbecher, S Staak, H Scheich, ED Gundelfinger, Eur J Neurosci 2003 18 942 950 10.1046/j.1460-9568.2003.02820.x 12925020
55. Abeta42-induced neurodegeneration via an age-dependent autophagic-lysosomal injury in Drosophila. D Ling, HJ Song, D Garza, TP Neufeld, PM Salvaterra, PLoS One 2009 4 4201 10.1371/journal.pone.0004201 19145255
56. Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of alpha-synuclein. D Ebrahimi-Fakhari, I Cantuti-Castelvetri, Z Fan, E Rockenstein, E Masliah, BT Hyman, PJ McLean, VK Unni, J Neurosci 2011 31 14508 14520 10.1523/JNEUROSCI. 1560-11.2011 21994367
57. Expression of A53T mutant but not wild-type alpha-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. L Stefanis, KE Larsen, HJ Rideout, D Sulzer, LA Greene, J Neurosci 2001 21 9549 9560 11739566
58. The ubiquitin pathway in Parkinson's disease. E Leroy, R Boyer, G Auburger, B Leube, G Ulm, E Mezey, G Harta, MJ Brownstein, S Jonnalagada, T Chernova, A Dehejia, C Lavedan, T Gasser, PJ Steinbach, KD Wilkinson, MH Polymeropoulos, Nature 1998 395 451 452 10.1038/26652 9774100
59. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. T Kitada, S Asakawa, N Hattori, H Matsumine, Y Yamamura, S Minoshima, M Yokochi, Y Mizuno, N Shimizu, Nature 1998 392 605 608 10.1038/33416 9560156
60. Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. H Shimura, MG Schlossmacher, N Hattori, MP Frosch, A Trockenbacher, R Schneider, Y Mizuno, KS Kosik, DJ Selkoe, Science 2001 293 263 269 10.1126/science.1060627 11431533
61. Impact of autosomal recessive juvenile Parkinson's disease mutations on the structure and interactions of the parkin ubiquitin-like domain. SS Safadi, KR Barber, GS Shaw, Biochemistry 2011 50 2603 2610 10.1021/bi200065g 21348451
62. Development and characterization of a new Parkinson's disease model resulting from impaired autophagy. I Ahmed, Y Liang, S Schools, VL Dawson, TM Dawson, JM Savitt, J Neurosci 2012 32 16503 16509 10.1523/JNEUROSCI.0209-12.2012 23152632
63. p62/SQSTM1-dependent autophagy of Lewy body-like alpha-synuclein inclusions. Y Watanabe, H Tatebe, K Taguchi, Y Endo, T Tokuda, T Mizuno, M Nakagawa, M Tanaka, PLoS One 2012 7 52868 10.1371/journal.pone.0052868 23300799
64. alpha-Synuclein impairs macroautophagy: implications for Parkinson's disease. AR Winslow, CW Chen, S Corrochano, A Acevedo-Arozena, DE Gordon, AA Peden, M Lichtenberg, FM Menzies, B Ravikumar, S Imarisio, S Brown, CJ O'Kane, DC Rubinsztein, J Cell Biol 2010 190 1023 1037 10.1083/jcb.201003122 20855506
65. Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. D Kirik, C Rosenblad, C Burger, C Lundberg, TE Johansen, N Muzyczka, RJ Mandel, A Bjorklund, J Neurosci 2002 22 2780 2791 11923443
66. Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics. I Irrcher, H Aleyasin, EL Seifert, SJ Hewitt, S Chhabra, M Phillips, AK Lutz, MW Rousseaux, L Bevilacqua, A Jahani-Asl, S Callaghan, JG MacLaurin, KF Winklhofer, P Rizzu, P Rippstein, RH Kim, CX Chen, EA Fon, RS Slack, ME Harper, HM McBride, TW Mak, DS Park, Hum Mol Genet 2010 19 3734 3746 10.1093/hmg/ddq288 20639397
67. Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells. ED Plowey, SJ Cherra 3rd, YJ Liu, CT Chu, J Neurochem 2008 105 1048 1056 10.1111/j.1471-4159.2008.05217.x 18182054
68. The Parkinson-associated protein PINK1 interacts with Beclin1 and promotes autophagy. S Michiorri, V Gelmetti, E Giarda, F Lombardi, F Romano, R Marongiu, S Nerini-Molteni, P Sale, R Vago, G Arena, L Torosantucci, L Cassina, MA Russo, B Dallapiccola, EM Valente, G Casari, Cell Death Differ 2010 17 962 974 10.1038/cdd.2009.200 20057503
69. Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson's and Lewy body diseases. B Spencer, R Potkar, M Trejo, E Rockenstein, C Patrick, R Gindi, A Adame, T Wyss-Coray, E Masliah, J Neurosci 2009 29 13578 13588 10.1523/JNEUROSCI.4390-09.2009 19864570
70. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. D Narendra, A Tanaka, DF Suen, RJ Youle, J Cell Biol 2008 183 795 803 10.1083/jcb.200809125 19029340
71. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. DP Narendra, SM Jin, A Tanaka, DF Suen, CA Gautier, J Shen, MR Cookson, RJ Youle, PLoS Biol 2010 8 1000298 10.1371/journal.pbio.1000298 20126261
72. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. S Geisler, KM Holmstrom, D Skujat, FC Fiesel, OC Rothfuss, PJ Kahle, W Springer, Nat Cell Biol 2010 12 119 131 10.1038/ncb2012 20098416
73. The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations. S Geisler, KM Holmstrom, A Treis, D Skujat, SS Weber, FC Fiesel, PJ Kahle, W Springer, Autophagy 2010 6 871 878 10.4161/auto.6.7.13286 20798600
74. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. JC Greene, AJ Whitworth, I Kuo, LA Andrews, MB Feany, LJ Pallanck, Proc Natl Acad Sci U S A 2003 100 4078 4083 10.1073/pnas.0737556100 12642658
75. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. CA Gautier, T Kitada, J Shen, Proc Natl Acad Sci U S A 2008 105 11364 11369 10.1073/pnas.0802076105 18687901
76. The antioxidant Trolox helps recovery from the familial Parkinson's disease-specific mitochondrial deficits caused by PINK1- and DJ-1-deficiency in dopaminergic neuronal cells. JH Shim, SH Yoon, KH Kim, JY Han, JY Ha, DH Hyun, SH Paek, UJ Kang, X Zhuang, JH Son, Mitochondrion 2011 11 707 715 10.1016/j.mito.2011.05.013 21664494
77. Lysosomal impairment in Parkinson's disease. B Dehay, M Martinez-Vicente, GA Caldwell, KA Caldwell, Z Yue, MR Cookson, C Klein, M Vila, E Bezard, Mov Disord 2013 28 725 732 10.1002/mds.25462 23580333
78. Deficiency of ATP13A2 leads to lysosomal dysfunction, alpha-synuclein accumulation, and neurotoxicity. M Usenovic, E Tresse, JR Mazzulli, JP Taylor, D Krainc, J Neurosci 2012 32 4240 4246 10.1523/JNEUROSCI.5575-11.2012 22442086
79. Atp13a2-deficient mice exhibit neuronal ceroid lipofuscinosis, limited alpha-synuclein accumulation and age-dependent sensorimotor deficits. PJ Schultheis, SM Fleming, AK Clippinger, J Lewis, T Tsunemi, B Giasson, DW Dickson, JR Mazzulli, ME Bardgett, KL Haik, O Ekhator, AK Chava, J Howard, M Gannon, E Hoffman, Y Chen, V Prasad, SC Linn, RJ Tamargo, W Westbroek, E Sidransky, D Krainc, GE Shull, Hum Mol Genet 2013 22 2067 2082 10.1093/hmg/ddt057 23393156
80. Making connections: pathology and genetics link amyotrophic lateral sclerosis with frontotemporal lobe dementia. F Fecto, T Siddique, J Mol Neurosci 2011 45 663 675 10.1007/s12031-011-9637-9 21901496
81. Motor neuron-specific disruption of proteasomes, but not autophagy, replicates amyotrophic lateral sclerosis. Y Tashiro, M Urushitani, H Inoue, M Koike, Y Uchiyama, M Komatsu, K Tanaka, M Yamazaki, M Abe, H Misawa, K Sakimura, H Ito, R Takahashi, J Biol Chem 2012 287 42984 42994 10.1074/jbc.M112.417600 23095749
82. Functional alterations of the ubiquitin-proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis. C Cheroni, M Marino, M Tortarolo, P Veglianese, S De Biasi, E Fontana, LV Zuccarello, CJ Maynard, NP Dantuma, C Bendotti, Hum Mol Genet 2009 18 82 96 18826962
83. Aggregate formation in the spinal cord of mutant SOD1 transgenic mice is reversible and mediated by proteasomes. K Puttaparthi, C Wojcik, B Rajendran, GN DeMartino, JL Elliott, J Neurochem 2003 87 851 860 14622116
84. Proteasomal degradation of mutant superoxide dismutases linked to amyotrophic lateral sclerosis. L Di Noto, LJ Whitson, X Cao, PJ Hart, RL Levine, J Biol Chem 2005 280 39907 39913 10.1074/jbc.M506247200 16195234
85. Proteasome inhibition enhances the stability of mouse Cu/Zn superoxide dismutase with mutations linked to familial amyotrophic lateral sclerosis. EK Hoffman, HM Wilcox, RW Scott, R Siman, J Neurol Sci 1996 139 15 20 10.1016/0022-510X(96)00031-7 8836967
86. Proteasomal inhibition causes the formation of protein aggregates containing a wide range of proteins, including nitrated proteins. DH Hyun, M Lee, B Halliwell, P Jenner, J Neurochem 2003 86 363 373 12871577
87. Formation of high molecular weight complexes of mutant Cu, Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis. JA Johnston, MJ Dalton, ME Gurney, RR Kopito, Proc Natl Acad Sci U S A 2000 97 12571 12576 10.1073/pnas.220417997 11050163
88. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. HX Deng, W Chen, ST Hong, KM Boycott, GH Gorrie, N Siddique, Y Yang, F Fecto, Y Shi, H Zhai, H Jiang, M Hirano, E Rampersaud, GH Jansen, S Donkervoort, EH Bigio, BR Brooks, K Ajroud, RL Sufit, JL Haines, E Mugnaini, MA Pericak-Vance, T Siddique, Nature 2011 477 211 215 10.1038/nature10353 21857683
89. SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. F Fecto, J Yan, SP Vemula, E Liu, Y Yang, W Chen, JG Zheng, Y Shi, N Siddique, H Arrat, S Donkervoort, S Ajroud-Driss, RL Sufit, SL Heller, HX Deng, T Siddique, Arch Neurol 2011 68 1440 1446 10.1001/archneurol.2011.250 22084127
90. Protein clearing pathways in ALS. M Ferrucci, F Fulceri, L Toti, P Soldani, G Siciliano, A Paparelli, F Fornai, Arch Ital Biol 2011 149 121 149 21412721
91. Lithium delays progression of amyotrophic lateral sclerosis. F Fornai, P Longone, L Cafaro, O Kastsiuchenka, M Ferrucci, ML Manca, G Lazzeri, A Spalloni, N Bellio, P Lenzi, N Modugno, G Siciliano, C Isidoro, L Murri, S Ruggieri, A Paparelli, Proc Natl Acad Sci U S A 2008 105 2052 2057 10.1073/pnas.0708022105 18250315
92. Sequestosome 1/p62 links familial ALS mutant SOD1 to LC3 via an ubiquitin-independent mechanism. J Gal, AL Strom, DM Kwinter, R Kilty, J Zhang, P Shi, W Fu, MW Wooten, H Zhu, J Neurochem 2009 111 1062 1073 10.1111/j.1471-4159.2009.06388.x 19765191
93. XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. C Hetz, P Thielen, S Matus, M Nassif, F Court, R Kiffin, G Martinez, AM Cuervo, RH Brown, LH Glimcher, Genes Dev 2009 23 2294 2306 10.1101/gad.1830709 19762508
94. Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis. X Zhang, L Li, S Chen, D Yang, Y Wang, Z Wang, W Le, Autophagy 2011 7 412 425 10.4161/auto.7.4.14541 21193837
95. Treatment with lithium carbonate does not improve disease progression in two different strains of SOD1 mutant mice. C Pizzasegola, I Caron, C Daleno, A Ronchi, C Minoia, MT Carri, C Bendotti, Amyotroph Lateral Scler 2009 10 221 228 10.1080/17482960902803440 19308767
96. No benefit from chronic lithium dosing in a sibling-matched, gender balanced, investigator-blinded trial using a standard mouse model of familial ALS. A Gill, J Kidd, F Vieira, K Thompson, S Perrin, PLoS One 2009 4 6489 10.1371/journal.pone.0006489 19649300
97. Lithium carbonate in amyotrophic lateral sclerosis: lack of efficacy in a dose-finding trial. A Chiò G Borghero, A Calvo, M Capasso, C Caponnetto, M Corbo, F Giannini, G Logroscino, J Mandrioli, N Marcello, L Mazzini, C Moglia, MR Monsurrò G Mora, F Patti, M Perini, V Pietrini, F Pisano, E Pupillo, M Sabatelli, F Salvi, V Silani, IL Simone, G Sorarù MR Tola, P Volanti, E Beghi, LITALS Study Group, Neurology 2010 75 619 625 10.1212/WNL.0b013e3181ed9e7c 20702794
98. Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons. K Castillo, M Nassif, V Valenzuela, F Rojas, S Matus, G Mercado, FA Court, B van Zundert, C Hetz, Autophagy 2013 9 1308 1320 10.4161/auto.25188 23851366
99. SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. E Rubino, I Rainero, A Chiò E Rogaeva, D Galimberti, P Fenoglio, Y Grinberg, G Isaia, A Calvo, S Gentile, AC Bruni, PH St George-Hyslop, E Scarpini, S Gallone, L Pinessi, TODEM Study Group, Neurology 2012 79 1556 1562 10.1212/WNL.0b013e31826e25df 22972638
100. PLIC proteins or ubiquilins regulate autophagy-dependent cell survival during nutrient starvation. EN N'Diaye, KK Kajihara, I Hsieh, H Morisaki, J Debnath, EJ Brown, EMBO Rep 2009 10 173 179 10.1038/embor.2008.238 19148225
101. Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. C Rothenberg, D Srinivasan, L Mah, S Kaushik, CM Peterhoff, J Ugolino, S Fang, AM Cuervo, RA Nixon, MJ Monteiro, Hum Mol Genet 2010 19 3219 3232 10.1093/hmg/ddq231 20529957
102. Ubiquilin at a crossroads in protein degradation pathways. C Rothenberg, MJ Monteiro, Autophagy 2010 6 979 980 10.4161/auto.6.7.13118 20729634
103. Physiological significance of selective degradation of p62 by autophagy. M Komatsu, Y Ichimura, FEBS Lett 2010 584 1374 1378 10.1016/j.febslet.2010.02. 017 20153326
104. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. S Pankiv, TH Clausen, T Lamark, A Brech, JA Bruun, H Outzen, A Overvatn, G Bjorkoy, T Johansen, J Biol Chem 2007 282 24131 24145 10.1074/jbc.M702824200 17580304
105. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. M Komatsu, S Waguri, M Koike, YS Sou, T Ueno, T Hara, N Mizushima, J Iwata, J Ezaki, S Murata, J Hamazaki, Y Nishito, S Iemura, T Natsume, T Yanagawa, J Uwayama, E Warabi, H Yoshida, T Ishii, A Kobayashi, M Yamamoto, Z Yue, Y Uchiyama, E Kominami, K Tanaka, Cell 2007 131 1149 1163 10.1016/j.cell.2007.10.035 18083104
106. Mutations of optineurin in amyotrophic lateral sclerosis. H Maruyama, H Morino, H Ito, Y Izumi, H Kato, Y Watanabe, Y Kinoshita, M Kamada, H Nodera, H Suzuki, O Komure, S Matsuura, K Kobatake, N Morimoto, K Abe, N Suzuki, M Aoki, A Kawata, T Hirai, T Kato, K Ogasawara, A Hirano, T Takumi, H Kusaka, K Hagiwara, R Kaji, H Kawakami, Nature 2010 465 223 226 10.1038/nature08971 20428114
107. Exome sequencing reveals VCP mutations as a cause of familial ALS. JO Johnson, J Mandrioli, M Benatar, Y Abramzon, VM Van Deerlin, JQ Trojanowski, JR Gibbs, M Brunetti, S Gronka, J Wuu, J Ding, L McCluskey, M Martinez-Lage, D Falcone, DG Hernandez, S Arepalli, S Chong, JC Schymick, J Rothstein, F Landi, YD Wang, A Calvo, G Mora, M Sabatelli, MR Monsurrò S Battistini, F Salvi, R Spataro, P Sola, G Borghero, G Galassi, SW Scholz, JP Taylor, G Restagno, A Chiò BJ Traynor, ITALSGEN Consortium, Neuron 2010 68 857 864 10.1016/j.neuron.2010.11.036 21145000
108. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. GD Watts, J Wymer, MJ Kovach, SG Mehta, S Mumm, D Darvish, A Pestronk, MP Whyte, VE Kimonis, Nat Genet 2004 36 377 381 10.1038/ng1332 15034582
109. Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. JS Ju, RA Fuentealba, SE Miller, E Jackson, D Piwnica-Worms, RH Baloh, CC Weihl, J Cell Biol 2009 187 875 888 10.1083/jcb.200908115 20008565
110. VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD. E Tresse, FA Salomons, J Vesa, LC Bott, V Kimonis, TP Yao, NP Dantuma, JP Taylor, Autophagy 2010 6 217 227 10.4161/auto.6.2.11014 20104022
111. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. P Wild, H Farhan, DG McEwan, S Wagner, VV Rogov, NR Brady, B Richter, J Korac, O Waidmann, C Choudhary, V Dötsch, D Bumann, I Dikic, Science 2011 333 228 233 10.1126/science.1205405 21617041
112. Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P2. CJ Ferguson, GM Lenk, MH Meisler, Hum Mol Genet 2009 18 4868 4878 10.1093/hmg/ddp460 19793721
113. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. G Skibinski, NJ Parkinson, JM Brown, L Chakrabarti, SL Lloyd, H Hummerich, JE Nielsen, JR Hodges, MG Spillantini, T Thusgaard, S Brandner, A Brun, MN Rossor, A Gade, P Johannsen, SA Sørensen, S Gydesen, EM Fisher, J Collinge, Nat Genet 2005 37 806 808 10.1038/ng1609 16041373
114. Degradation of TDP-43 and its pathogenic form by autophagy and the ubiquitin-proteasome system. X Wang, H Fan, Z Ying, B Li, H Wang, G Wang, Neurosci Lett 2010 469 112 116 10.1016/j.neulet.2009.11.055 19944744
115. Synergistic effect between proteasome and autophagosome in the clearance of polyubiquitinated TDP-43. M Urushitani, T Sato, H Bamba, Y Hisa, I Tooyama, J Neurosci Res 2010 88 784 797 19798749
116. Regulation of TDP-43 aggregation by phosphorylation and p62/SQSTM1. OA Brady, P Meng, Y Zheng, Y Mao, F Hu, J Neurochem 2011 116 248 259 10.1111/j.1471-4159.2010.07098.x 21062285
117. VCP mutations causing frontotemporal lobar degeneration disrupt localization of TDP-43 and induce cell death. MA Gitcho, J Strider, D Carter, L Taylor-Reinwald, MS Forman, AM Goate, NJ Cairns, J Biol Chem 2009 284 12384 12398 10.1074/jbc.M900992200 19237541
118. Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. M Filimonenko, S Stuffers, C Raiborg, A Yamamoto, L Malerod, EM Fisher, A Isaacs, A Brech, H Stenmark, A Simonsen, J Cell Biol 2007 179 485 500 10.1083/jcb.200702115 17984323
119. Potentiation of amyotrophic lateral sclerosis (ALS)-associated TDP-43 aggregation by the proteasome-targeting factor, ubiquilin 1. SH Kim, Y Shi, KA Hanson, LM Williams, R Sakasai, MJ Bowler, RS Tibbetts, J Biol Chem 2009 284 8083 8092 10.1074/jbc.M808064200 19112176
120. Ubiquilin modifies TDP-43 toxicity in a Drosophila model of amyotrophic lateral sclerosis (ALS). KA Hanson, SH Kim, DA Wassarman, RS Tibbetts, J Biol Chem 2010 285 11068 11072 10.1074/jbc.C109.078527 20154090
121. The ubiquitin-proteasome system in Huntington's disease: are proteasomes impaired, initiators of disease, or coming to the rescue? S Schipper-Krom, K Juenemann, EA Reits, Biochem Res Int 2012 2012 837015 23050151
122. Unbiased screen reveals ubiquilin-1 and -2 highly associated with huntingtin inclusions. NJ Rutherford, J Lewis, AK Clippinger, MA Thomas, J Adamson, PE Cruz, A Cannon, G Xu, TE Golde, G Shaw, DR Borchelt, BI Giasson, Brain Res 2013 1524 62 73 23774650
123. Studies on brain biopsies of patients with Huntington's chorea. I Tellez-Nagel, AB Johnson, RD Terry, J Neuropathol Exp Neurol 1974 33 308 332 10.1097/00005072-197404000-00008 4150800
124. Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy. KB Kegel, M Kim, E Sapp, C McIntyre, JG Castano, N Aronin, M DiFiglia, J Neurosci 2000 20 7268 7278 11007884
125. A stress sensitive ER membrane-association domain in Huntingtin protein defines a potential role for Huntingtin in the regulation of autophagy. RS Atwal, R Truant, Autophagy 2008 4 91 93 17986868
126. Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease. M Martinez-Vicente, Z Talloczy, E Wong, G Tang, H Koga, S Kaushik, R de Vries, E Arias, S Harris, D Sulzer, AM Cuervo, Nat Neurosci 2010 13 567 576 10.1038/nn.2528 20383138
127. Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. M Shibata, T Lu, T Furuya, A Degterev, N Mizushima, T Yoshimori, M MacDonald, B Yankner, J Yuan, J Biol Chem 2006 281 14474 14485 10.1074/jbc.M600364200 16522639
128. Raised intracellular glucose concentrations reduce aggregation and cell death caused by mutant huntingtin exon 1 by decreasing mTOR phosphorylation and inducing autophagy. B Ravikumar, A Stewart, H Kita, K Kato, R Duden, DC Rubinsztein, Hum Mol Genet 2003 12 985 994 10.1093/hmg/ddg109 12700167
129. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. B Ravikumar, C Vacher, Z Berger, JE Davies, S Luo, LG Oroz, F Scaravilli, DF Easton, R Duden, CJ O'Kane, DC Rubinsztein, Nat Genet 2004 36 585 595 10.1038/ng1362 15146184
130. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. S Sarkar, EO Perlstein, S Imarisio, S Pineau, A Cordenier, RL Maglathlin, JA Webster, TA Lewis, CJ O'Kane, SL Schreiber, DC Rubinsztein, Nat Chem Biol 2007 3 331 338 10.1038/nchembio883 17486044
131. TOR on the brain. MG Garelick, BK Kennedy, Exp Gerontol 2011 46 155 163 10.1016/j.exger.2010.08.030 20849946