{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T01:32:59Z","timestamp":1775784779883,"version":"3.50.1"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"7113","license":[{"start":{"date-parts":[[2006,10,1]],"date-time":"2006-10-01T00:00:00Z","timestamp":1159660800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2006,10]]},"DOI":"10.1038\/nature05291","type":"journal-article","created":{"date-parts":[[2006,10,18]],"date-time":"2006-10-18T22:42:29Z","timestamp":1161211349000},"page":"780-786","source":"Crossref","is-referenced-by-count":1339,"title":["The roles of intracellular protein-degradation pathways in neurodegeneration"],"prefix":"10.1038","volume":"443","author":[{"given":"David C.","family":"Rubinsztein","sequence":"first","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2006,10,18]]},"reference":[{"key":"BFnature05291_CR1","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1126\/science.1067122","volume":"296","author":"JP Taylor","year":"2002","unstructured":"Taylor, J. P., Hardy, J. & Fischbeck, K. H. Toxic proteins in neurodegenerative disease. Science 296, 1991\u20131995 (2002).","journal-title":"Science"},{"key":"BFnature05291_CR2","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1038\/nrm1742","volume":"6","author":"CA Ross","year":"2005","unstructured":"Ross, C. A. & Poirier, M. A. What is the role of protein aggregation in neurodegeneration? Nature Rev. Mol. Cell Biol. 6, 891\u2013898 (2005).","journal-title":"Nature Rev. Mol. Cell Biol."},{"key":"BFnature05291_CR3","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/35084141","volume":"412","author":"MF Perutz","year":"2001","unstructured":"Perutz, M. F. & Windle, A. H. Cause of neural death in neurodegenerative diseases attributable to expansion of glutamine repeats. Nature 412, 143\u2013144 (2001).","journal-title":"Nature"},{"key":"BFnature05291_CR4","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1042\/BST0330553","volume":"33","author":"MN Pangalos","year":"2005","unstructured":"Pangalos, M. N., Jacobsen, S. J. & Reinhart, P. H. Disease modifying strategies for the treatment of Alzheimer's disease targeted at modulating levels of the \u03b2-amyloid peptide. Biochem. Soc. Trans. 33, 553\u2013558 (2005).","journal-title":"Biochem. Soc. Trans."},{"key":"BFnature05291_CR5","doi-asserted-by":"publisher","first-page":"7862","DOI":"10.1523\/JNEUROSCI.22-18-07862.2002","volume":"22","author":"CL Wellington","year":"2002","unstructured":"Wellington, C. L. et al. Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease. J. Neurosci. 22, 7862\u20137872 (2002).","journal-title":"J. Neurosci."},{"key":"BFnature05291_CR6","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1083\/jcb.200412071","volume":"169","author":"S Luo","year":"2005","unstructured":"Luo, S., Vacher, C., Davies, J. E. & Rubinsztein, D. C. Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity. J. Cell Biol. 169, 647\u2013656 (2005).","journal-title":"J. Cell Biol."},{"key":"BFnature05291_CR7","doi-asserted-by":"publisher","first-page":"9158","DOI":"10.1074\/jbc.273.15.9158","volume":"273","author":"CL Wellington","year":"1998","unstructured":"Wellington, C. L. et al. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J. Biol. Chem. 273, 9158\u20139167 (1998).","journal-title":"J. Biol. Chem."},{"key":"BFnature05291_CR8","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1212\/01.wnl.0000192261.02023.b8","volume":"66","author":"A Ciechanover","year":"2006","unstructured":"Ciechanover, A. The ubiquitin proteolytic system: from a vague idea, through basic mechanisms, and onto human diseases and drug targeting. Neurology 66, S7\u2013S19 (2006).","journal-title":"Neurology"},{"key":"BFnature05291_CR9","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.cell.2004.11.013","volume":"120","author":"H Richly","year":"2005","unstructured":"Richly, H. et al. A series of ubiquitin binding factors connects CDC48\/p97 to substrate multiubiquitylation and proteasomal targeting. Cell 120, 73\u201384 (2005).","journal-title":"Cell"},{"key":"BFnature05291_CR10","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1093\/hmg\/ddi426","volume":"15","author":"CC Weihl","year":"2006","unstructured":"Weihl, C. C., Dalal, S., Pestronk, A. & Hanson, P. I. Inclusion body myopathy-associated mutations in p97\/VCP impair endoplasmic reticulum-associated degradation. Hum. Mol. Genet. 15, 189\u2013199 (2006).","journal-title":"Hum. Mol. Genet."},{"key":"BFnature05291_CR11","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1093\/hmg\/11.9.1107","volume":"11","author":"B Ravikumar","year":"2002","unstructured":"Ravikumar, B., Duden, R. & Rubinsztein, D. C. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum. Mol. Genet. 11, 1107\u20131117 (2002).","journal-title":"Hum. Mol. Genet."},{"key":"BFnature05291_CR12","doi-asserted-by":"publisher","first-page":"25009","DOI":"10.1074\/jbc.M300227200","volume":"278","author":"JL Webb","year":"2003","unstructured":"Webb, J. L., Ravikumar, B., Atkins, J., Skepper, J. N. & Rubinsztein, D. C. \u03b1-Synuclein is degraded by both autophagy and the proteasome. J. Biol. Chem. 278, 25009\u201325013 (2003).","journal-title":"J. Biol. Chem."},{"key":"BFnature05291_CR13","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.1093\/hmg\/11.22.2689","volume":"11","author":"LG Verhoef","year":"2002","unstructured":"Verhoef, L. G., Lindsten, K., Masucci, M. G. & Dantuma, N. P. Aggregate formation inhibits proteasomal degradation of polyglutamine proteins. Hum. Mol. Genet. 11, 2689\u20132700 (2002).","journal-title":"Hum. Mol. Genet."},{"key":"BFnature05291_CR14","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S1097-2765(04)00151-0","volume":"14","author":"P Venkatraman","year":"2004","unstructured":"Venkatraman, P., Wetzel, R., Tanaka, M., Nukina, N. & Goldberg, A. L. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins. Mol. Cell 14, 95\u2013104 (2004).","journal-title":"Mol. Cell"},{"key":"BFnature05291_CR15","doi-asserted-by":"publisher","first-page":"4307","DOI":"10.1038\/sj.emboj.7600426","volume":"23","author":"CI Holmberg","year":"2004","unstructured":"Holmberg, C. I., Staniszewski, K. E., Mensah, K. N., Matouschek, A. & Morimoto, R. I. Inefficient degradation of truncated polyglutamine proteins by the proteasome. EMBO J. 23, 4307\u20134318 (2004).","journal-title":"EMBO J."},{"key":"BFnature05291_CR16","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1038\/sj.cdd.4401765","volume":"12","author":"T Yorimitsu","year":"2005","unstructured":"Yorimitsu, T. & Klionsky, D. J. Autophagy: molecular machinery for self-eating. Cell Death Differ. 12, 1542\u20131552 (2005).","journal-title":"Cell Death Differ."},{"key":"BFnature05291_CR17","doi-asserted-by":"publisher","first-page":"14474","DOI":"10.1074\/jbc.M600364200","volume":"281","author":"M Shibata","year":"2006","unstructured":"Shibata, M. et al. Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J. Biol. Chem. 281, 14474\u201314485 (2006).","journal-title":"J. Biol. Chem."},{"key":"BFnature05291_CR18","doi-asserted-by":"publisher","first-page":"13135","DOI":"10.1073\/pnas.0505801102","volume":"102","author":"A Iwata","year":"2005","unstructured":"Iwata, A. et al. Increased susceptibility of cytoplasmic over nuclear polyglutamine aggregates to autophagic degradation. Proc. Natl Acad. Sci. USA 102, 13135\u201313140 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature05291_CR19","doi-asserted-by":"publisher","first-page":"3231","DOI":"10.1093\/hmg\/ddg346","volume":"12","author":"ZH Qin","year":"2003","unstructured":"Qin, Z. H. et al. Autophagy regulates the processing of amino terminal huntingtin fragments. Hum. Mol. Genet. 12, 3231\u20133244 (2003).","journal-title":"Hum. Mol. Genet."},{"key":"BFnature05291_CR20","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1093\/hmg\/ddi458","volume":"15","author":"Z Berger","year":"2006","unstructured":"Berger, Z. et al. Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum. Mol. Genet. 15, 433\u2013442 (2006).","journal-title":"Hum. Mol. Genet."},{"key":"BFnature05291_CR21","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/ng1362","volume":"36","author":"B Ravikumar","year":"2004","unstructured":"Ravikumar, B. et al. mTOR inhibition induces autophagy and reduces toxicity of the Huntington's disease mutation in Drosophila and mouse models. Nature Genet. 36, 585\u2013595 (2004).","journal-title":"Nature Genet."},{"key":"BFnature05291_CR22","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1083\/jcb.200412022","volume":"169","author":"M Komatsu","year":"2005","unstructured":"Komatsu, M. et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol. 169, 425\u2013434 (2005).","journal-title":"J. Cell Biol."},{"key":"BFnature05291_CR23","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1093\/hmg\/ddg109","volume":"12","author":"B Ravikumar","year":"2003","unstructured":"Ravikumar, B. et al. Raised intracellular glucose concentrations reduce aggregation and cell death caused by mutant huntingtin exon 1 by decreasing mTOR phosphorylation and inducing autophagy. Hum. Mol. Genet. 12, 985\u2013994 (2003).","journal-title":"Hum. Mol. Genet."},{"key":"BFnature05291_CR24","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1016\/j.biocel.2004.05.008","volume":"36","author":"H Rideout","year":"2004","unstructured":"Rideout, H., Lang-Rollin, I. & Stefanis, L. Involvement of macroautophagy in the dissolution of neuronal inclusions. Int. J. Biochem. Cell Biol. 36, 2551\u20132562 (2004).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"BFnature05291_CR25","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1016\/j.biocel.2004.04.010","volume":"36","author":"A Massey","year":"2004","unstructured":"Massey, A., Kiffin, R. & Cuervo, A. M. Pathophysiology of chaperone-mediated autophagy. Int. J. Biochem. Cell Biol. 36, 2420\u20132434 (2004).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"BFnature05291_CR26","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1006\/exnr.2002.8050","volume":"179","author":"KS McNaught","year":"2003","unstructured":"McNaught, K. S., Belizaire, R., Isacson, O., Jenner, P. & Olanow, C. W. Altered proteasomal function in sporadic Parkinson's disease. Exp. Neurol. 179, 38\u201346 (2003).","journal-title":"Exp. Neurol."},{"key":"BFnature05291_CR27","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/ana.20207","volume":"56","author":"H Seo","year":"2004","unstructured":"Seo, H., Sonntag, K. C. & Isacson, O. Generalized brain and skin proteasome inhibition in Huntington's disease. Ann. Neurol. 56, 319\u2013328 (2004).","journal-title":"Ann. Neurol."},{"key":"BFnature05291_CR28","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1126\/science.292.5521.1552","volume":"292","author":"NF Bence","year":"2001","unstructured":"Bence, N. F., Sampat, R. M. & Kopito, R. R. Impairment of the ubiquitin\u2013proteasome system by protein aggregation. Science 292, 1552\u20131555 (2001).","journal-title":"Science"},{"key":"BFnature05291_CR29","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1093\/hmg\/ddi064","volume":"14","author":"AB Bowman","year":"2005","unstructured":"Bowman, A. B., Yoo, S. Y., Dantuma, N. P. & Zoghbi, H. Y. Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin\u2013proteasome system impairment and inversely correlates with a degree of nuclear inclusion formation. Hum. Mol. Genet. 14, 679\u2013691 (2005).","journal-title":"Hum. Mol. Genet."},{"key":"BFnature05291_CR30","doi-asserted-by":"publisher","first-page":"11653","DOI":"10.1523\/JNEUROSCI.23-37-11653.2003","volume":"23","author":"M Diaz-Hernandez","year":"2003","unstructured":"Diaz-Hernandez, M. et al. Neuronal induction of the immunoproteasome in Huntington's disease. J. Neurosci. 23, 11653\u201311661 (2003).","journal-title":"J. Neurosci."},{"key":"BFnature05291_CR31","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S1097-2765(04)00156-X","volume":"14","author":"XM Sun","year":"2004","unstructured":"Sun, X. M. et al. Caspase activation inhibits proteasome function during apoptosis. Mol. Cell 14, 81\u201393 (2004).","journal-title":"Mol. Cell"},{"key":"BFnature05291_CR32","doi-asserted-by":"publisher","first-page":"13354","DOI":"10.1073\/pnas.240347797","volume":"97","author":"Y Zhang","year":"2000","unstructured":"Zhang, Y. et al. Parkin functions as an E2-dependent ubiquitin\u2013protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc. Natl Acad. Sci. USA 97, 13354\u201313359 (2000).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature05291_CR33","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/77060","volume":"25","author":"H Shimura","year":"2000","unstructured":"Shimura, H. et al. Familial Parkinson disease gene product, parkin, is a ubiquitin\u2013protein ligase. Nature Genet. 25, 302\u2013305 (2000).","journal-title":"Nature Genet."},{"key":"BFnature05291_CR34","doi-asserted-by":"publisher","first-page":"35661","DOI":"10.1074\/jbc.C000447200","volume":"275","author":"Y Imai","year":"2000","unstructured":"Imai, Y., Soda, M. & Takahashi, R. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin\u2013protein ligase activity. J. Biol. Chem. 275, 35661\u201335664 (2000).","journal-title":"J. Biol. Chem."},{"key":"BFnature05291_CR35","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/26652","volume":"395","author":"E Leroy","year":"1998","unstructured":"Leroy, E. et al. The ubiquitin pathway in Parkinson's disease. Nature 395, 451\u2013452 (1998).","journal-title":"Nature"},{"key":"BFnature05291_CR36","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1146\/annurev.neuro.28.061604.135718","volume":"28","author":"DJ Moore","year":"2005","unstructured":"Moore, D. J., West, A. B., Dawson, V. L. & Dawson, T. M. Molecular pathophysiology of Parkinson's disease. Annu. Rev. Neurosci. 28, 57\u201387 (2005).","journal-title":"Annu. Rev. Neurosci."},{"key":"BFnature05291_CR37","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1002\/ana.20757","volume":"59","author":"DG Healy","year":"2006","unstructured":"Healy, D. G. et al. UCHL-1 is not a Parkinson's disease susceptibility gene. Ann. Neurol. 59, 627\u2013633 (2006).","journal-title":"Ann. Neurol."},{"key":"BFnature05291_CR38","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S0092-8674(02)01012-7","volume":"111","author":"Y Liu","year":"2002","unstructured":"Liu, Y., Fallon, L., Lashuel, H. A., Liu, Z. & Lansbury, P. T. The UCH-L1 gene encodes two opposing enzymatic activities that affect \u03b1-synuclein degradation and Parkinson's disease susceptibility. Cell 111, 209\u2013218 (2002).","journal-title":"Cell"},{"key":"BFnature05291_CR39","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/12647","volume":"23","author":"K Saigoh","year":"1999","unstructured":"Saigoh, K. et al. Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice. Nature Genet. 23, 47\u201351 (1999).","journal-title":"Nature Genet."},{"key":"BFnature05291_CR40","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/ng1332","volume":"36","author":"GD Watts","year":"2004","unstructured":"Watts, G. D. et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nature Genet. 36, 377\u2013381 (2004).","journal-title":"Nature Genet."},{"key":"BFnature05291_CR41","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1002\/ana.20186","volume":"56","author":"KS McNaught","year":"2004","unstructured":"McNaught, K. S., Perl, D. P., Brownell, A. L. & Olanow, C. W. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. Ann. Neurol. 56, 149\u2013162 (2004).","journal-title":"Ann. Neurol."},{"key":"BFnature05291_CR42","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1038\/nature03029","volume":"432","author":"A Kuma","year":"2004","unstructured":"Kuma, A. et al. The role of autophagy during the early neonatal starvation period. Nature 432, 1032\u20131036 (2004).","journal-title":"Nature"},{"key":"BFnature05291_CR43","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1128\/MCB.25.3.1025-1040.2005","volume":"25","author":"P Boya","year":"2005","unstructured":"Boya, P. et al. Inhibition of macroautophagy triggers apoptosis. Mol. Cell Biol. 25, 1025\u20131040 (2005).","journal-title":"Mol. Cell Biol."},{"key":"BFnature05291_CR44","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1093\/hmg\/ddl036","volume":"15","author":"B Ravikumar","year":"2006","unstructured":"Ravikumar, B., Berger, Z., Vacher, C., O'Kane, C. J. & Rubinsztein, D. C. Rapamycin pre-treatment protects against apoptosis. Hum. Mol. Genet. 15, 1209\u20131216 (2006).","journal-title":"Hum. Mol. Genet."},{"key":"BFnature05291_CR45","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/nature04723","volume":"441","author":"M Komatsu","year":"2006","unstructured":"Komatsu, M. et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880\u2013884 (2006).","journal-title":"Nature"},{"key":"BFnature05291_CR46","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/nature04724","volume":"441","author":"T Hara","year":"2006","unstructured":"Hara, T. et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885\u2013889 (2006).","journal-title":"Nature"},{"key":"BFnature05291_CR47","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/ng1591","volume":"37","author":"B Ravikumar","year":"2005","unstructured":"Ravikumar, B. et al. Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nature Genet. 37, 771\u2013776 (2005).","journal-title":"Nature Genet."},{"key":"BFnature05291_CR48","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1083\/jcb.200511068","volume":"172","author":"JR Levy","year":"2006","unstructured":"Levy, J. R. et al. A motor neuron disease-associated mutation in p150Glued perturbs dynactin function and induces protein aggregation. J. Cell Biol. 172, 733\u2013745 (2006).","journal-title":"J. Cell Biol."},{"key":"BFnature05291_CR49","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/ng1123","volume":"33","author":"I Puls","year":"2003","unstructured":"Puls, I. et al. Mutant dynactin in motor neuron disease. Nature Genet. 33, 455\u2013456 (2003).","journal-title":"Nature Genet."},{"key":"BFnature05291_CR50","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1126\/science.1083129","volume":"300","author":"M Hafezparast","year":"2003","unstructured":"Hafezparast, M. et al. Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300, 808\u2013812 (2003).","journal-title":"Science"},{"key":"BFnature05291_CR51","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1083\/jcb.200501085","volume":"169","author":"D Kieran","year":"2005","unstructured":"Kieran, D. et al. A mutation in dynein rescues axonal transport defects and extends the life span of ALS mice. J. Cell Biol. 169, 561\u2013567 (2005).","journal-title":"J. Cell Biol."},{"key":"BFnature05291_CR52","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1097\/00001756-200504250-00002","volume":"16","author":"LA Ligon","year":"2005","unstructured":"Ligon, L. A. et al. Mutant superoxide dismutase disrupts cytoplasmic dynein in motor neurons. Neuroreport 16, 533\u2013536 (2005).","journal-title":"Neuroreport"},{"key":"BFnature05291_CR53","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1126\/science.1101738","volume":"305","author":"AM Cuervo","year":"2004","unstructured":"Cuervo, A. M., Stefansi, L., Fredenburg, R., Lansbury, P. T. & Sulzer, D. Impaired degradation of mutant \u03b1-synuclein by chaperone-mediated autophagy. Science 305, 1292\u20131295 (2004).","journal-title":"Science"},{"key":"BFnature05291_CR54","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.1073\/pnas.0501507102","volume":"102","author":"SQ Harper","year":"2005","unstructured":"Harper, S. Q. et al. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc. Natl Acad. Sci. USA 102, 5820\u20135825 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature05291_CR55","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/sj.gt.3302702","volume":"13","author":"E Rodriguez-Lebron","year":"2006","unstructured":"Rodriguez-Lebron, E. & Paulson, H. L. Allele-specific RNA interference for neurological disease. Gene. Ther. 13, 576\u2013581 (2006).","journal-title":"Gene. Ther."},{"key":"BFnature05291_CR56","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/hmg\/ddi422","volume":"15","author":"JE Davies","year":"2006","unstructured":"Davies, J. E., Sarkar, S. & Rubinsztein, D. C. Trehalose reduces aggregate formation and delays pathology in a transgenic mouse model of oculopharyngeal muscular dystrophy. Hum. Mol. Genet. 15, 23\u201331 (2006).","journal-title":"Hum. Mol. Genet."},{"key":"BFnature05291_CR57","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nature01301","volume":"421","author":"I Sanchez","year":"2003","unstructured":"Sanchez, I., Mahlke, C. & Yuan, Y. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders. Nature 421, 373\u2013379 (2003).","journal-title":"Nature"},{"key":"BFnature05291_CR58","doi-asserted-by":"publisher","first-page":"8772","DOI":"10.1523\/JNEUROSCI.21-22-08772.2001","volume":"21","author":"E Martin-Aparicio","year":"2001","unstructured":"Martin-Aparicio, E. et al. Proteasomal-dependent aggregate reversal and absence of cell death in a conditional mouse model of Huntington's disease. J. Neurosci. 21, 8772\u20138781 (2001).","journal-title":"J. Neurosci."},{"key":"BFnature05291_CR59","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1083\/jcb.200510065","volume":"172","author":"A Yamamoto","year":"2006","unstructured":"Yamamoto, A., Cremona, M. L. & Rothman, J. E. Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway. J. Cell Biol. 172, 719\u2013731 (2006).","journal-title":"J. Cell Biol."},{"key":"BFnature05291_CR60","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","volume":"277","author":"M DiFiglia","year":"1997","unstructured":"DiFiglia, M. et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990\u20131993 (1997).","journal-title":"Science"},{"key":"BFnature05291_CR61","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1089\/ars.2006.8.152","volume":"8","author":"R Kiffin","year":"2006","unstructured":"Kiffin, R., Bandyopadhyay, U. & Cuervo, A. Oxidative stress and autophagy. Antioxid. Redox Signal. 8, 152\u2013162 (2006).","journal-title":"Antioxid. Redox Signal."},{"key":"BFnature05291_CR62","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1038\/nature02998","volume":"431","author":"M Arrasate","year":"2004","unstructured":"Arrasate, M., Mitra, S., Schweitzer, E. S., Segal, M. R. & Finkbeiner, S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431, 805\u2013810 (2004).","journal-title":"Nature"},{"key":"BFnature05291_CR63","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1111\/j.1440-1797.2005.00493.x","volume":"10","author":"VW Lee","year":"2005","unstructured":"Lee, V. W. & Chapman, J. R. Sirolimus: its role in nephrology. Nephrology (Carlton) 10, 606\u2013614 (2005).","journal-title":"Nephrology (Carlton)"},{"key":"BFnature05291_CR64","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nrc1362","volume":"4,","author":"MA Bjornsti","year":"2004","unstructured":"Bjornsti, M. A. & Houghton, P. J. The TOR pathway: a target for cancer therapy. Nature Rev. Cancer 4, 335\u2013348 (2004).","journal-title":"Nature Rev. Cancer"},{"key":"BFnature05291_CR65","doi-asserted-by":"publisher","first-page":"5294","DOI":"10.1200\/JCO.2005.23.622","volume":"23","author":"E Galanis","year":"2005","unstructured":"Galanis, E. et al. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J. Clin. Oncol. 23, 5294\u20135304 (2005).","journal-title":"J. Clin. Oncol."},{"key":"BFnature05291_CR66","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","volume":"124","author":"S Wullschleger","year":"2006","unstructured":"Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471\u2013484 (2006).","journal-title":"Cell"},{"key":"BFnature05291_CR67","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1083\/jcb.200504035","volume":"170","author":"S Sarkar","year":"2005","unstructured":"Sarkar, S. et al. Lithium induces autophagy by inhibiting inositol monophosphatase. J. Cell Biol. 170, 1101\u20131111 (2005).","journal-title":"J. Cell Biol."},{"key":"BFnature05291_CR68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0005-2728(00)00234-6","volume":"1504","author":"MP Murphy","year":"2001","unstructured":"Murphy, M. P. How understanding the control of energy metabolism can help investigation of mitochondrial dysfunction, regulation and pharmacology. Biochim. Biophys. Acta 1504, 1\u201311 (2001).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnature05291_CR69","doi-asserted-by":"publisher","first-page":"20722","DOI":"10.1074\/jbc.M413934200","volume":"280","author":"J Pyo","year":"2005","unstructured":"Pyo, J. et al. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J. Biol. Chem. 280, 20722\u201320728 (2005).","journal-title":"J. Biol. Chem."},{"key":"BFnature05291_CR70","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/0092-8674(95)90542-1","volume":"81","author":"J Nasir","year":"1995","unstructured":"Nasir, J. et al. Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioural and morphological changes in heterozygotes. Cell 81, 811\u2013823 (1995).","journal-title":"Cell"},{"key":"BFnature05291_CR71","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/ng1095-155","volume":"11","author":"S Zeitlin","year":"1995","unstructured":"Zeitlin, S. et al. Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homolog. Nature Genet. 11, 155\u2013163 (1995).","journal-title":"Nature Genet."},{"key":"BFnature05291_CR72","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1126\/science.7618107","volume":"269","author":"MP Duyao","year":"1995","unstructured":"Duyao, M. P. et al. Inactivation of the mouse Huntington's disease gene homolog Hdh. Science 269, 407\u2013410 (1995).","journal-title":"Science"},{"key":"BFnature05291_CR73","volume-title":"Huntington's Disease","author":"PS Harper","year":"1996","unstructured":"Harper, P. S. Huntington's Disease 2nd edn (WB Saunders, London, 1996)."},{"key":"BFnature05291_CR74","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/S0168-9525(01)02625-7","volume":"18","author":"DC Rubinsztein","year":"2002","unstructured":"Rubinsztein, D. C. Lessons from animal models of Huntington's disease. Trends Genet. 18, 202\u2013209 (2002).","journal-title":"Trends Genet."},{"key":"BFnature05291_CR75","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/S0092-8674(00)80464-X","volume":"91","author":"JM Ordway","year":"1997","unstructured":"Ordway, J. M. et al. Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. Cell 91, 753\u2013763 (1997).","journal-title":"Cell"},{"key":"BFnature05291_CR76","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1038\/nrn1806","volume":"6","author":"E Cattaneo","year":"2005","unstructured":"Cattaneo, E., Zuccato, C. & Tartari, M. Normal huntingtin function: an alternative approach to Huntington's disease. Nature Rev. Neurosci. 6, 919\u2013930 (2005).","journal-title":"Nature Rev. Neurosci."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature05291.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature05291","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature05291.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T18:00:12Z","timestamp":1684432812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature05291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10]]},"references-count":76,"journal-issue":{"issue":"7113","published-print":{"date-parts":[[2006,10]]}},"alternative-id":["BFnature05291"],"URL":"https:\/\/doi.org\/10.1038\/nature05291","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10]]}}}