{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:23:05Z","timestamp":1792264985276,"version":"4.4.0"},"reference-count":139,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010969","name":"Alzheimer Nederland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010969","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Huntington\u2019s disease (HD) is a neurodegenerative disorder caused by the aggregation of the mutant huntingtin (mHTT) protein in nerve cells. mHTT self-aggregates to form soluble oligomers and insoluble fibrils, which interfere in a number of key cellular functions. This leads to cell quiescence and ultimately cell death. There are currently still no treatments available for HD, but approaches targeting the HTT levels offer systematic, mechanism-driven routes towards curing HD and other neurodegenerative diseases. This review summarizes the current state of knowledge of the mRNA targeting approaches such as antisense oligonucleotides and RNAi system; and the novel methods targeting mHTT and aggregates for degradation via the ubiquitin proteasome or the autophagy-lysosomal systems. These methods include the proteolysis-targeting chimera, Trim-Away, autophagosome-tethering compound, autophagy-targeting chimera, lysosome-targeting chimera and approach targeting mHTT for chaperone-mediated autophagy. These molecular strategies provide a knowledge-based approach to target HD and other neurodegenerative diseases at the origin.<\/jats:p>","DOI":"10.3389\/fmolb.2021.769184","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T06:35:20Z","timestamp":1636698920000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":87,"title":["Molecular Strategies to Target Protein Aggregation in Huntington\u2019s Disease"],"prefix":"10.3389","volume":"8","author":[{"given":"Olga D.","family":"Jarosi\u0144ska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan G. D.","family":"R\u00fcdiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1038\/s41589-021-00770-1","article-title":"LYTACs that Engage the Asialoglycoprotein Receptor for Targeted Protein Degradation","volume":"17","author":"Ahn","year":"2021","journal-title":"Nature Chemical Biology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1038\/s41587-019-0205-0","article-title":"A Divalent siRNA Chemical Scaffold for Potent and Sustained Modulation of Gene Expression throughout the central Nervous System","volume":"37","author":"Alterman","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1021\/acsmedchemlett.0c00556","article-title":"Solution Conformations Shed Light on PROTAC Cell Permeability","volume":"12","author":"Atilaw","year":"2021","journal-title":"ACS Med. Chem. Lett."},{"key":"B4","doi-asserted-by":"publisher","first-page":"E5427","DOI":"10.1073\/pnas.1516217112","article-title":"Transcellular Spreading of Huntingtin Aggregates in the Drosophila Brain","volume":"112","author":"Babcock","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B5","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41586-020-2545-9","article-title":"Lysosome-targeting Chimaeras for Degradation of Extracellular Proteins","volume":"584","author":"Banik","year":"2020","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1093\/hmg\/ddu504","article-title":"Comparative Study of Naturally Occurring Huntingtin Fragments in Drosophila Points to Exon 1 as the Most Pathogenic Species in Huntington's Disease","volume":"24","author":"Barbaro","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/nbt.1608","article-title":"Harnessing Chaperone-Mediated Autophagy for the Selective Degradation of Mutant Huntingtin Protein","volume":"28","author":"Bauer","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.cell.2017.08.009","article-title":"In Situ Architecture and Cellular Interactions of PolyQ Inclusions","volume":"171","author":"B\u00e4uerlein","year":"2017","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1002\/ana.20624","article-title":"Mitochondria Take center Stage in Aging and Neurodegeneration","volume":"58","author":"Beal","year":"2005","journal-title":"Ann. Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.jmb.2005.10.053","article-title":"Oligoproline Effects on Polyglutamine Conformation and Aggregation","volume":"355","author":"Bhattacharyya","year":"2006","journal-title":"J. Mol. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1089\/hum.2007.116","article-title":"Identification and Allele-specific Silencing of the Mutant Huntingtin Allele in Huntington's Disease Patient-Derived Fibroblasts","volume":"19","author":"Bilsen","year":"2008","journal-title":"Hum. Gene Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"4722","DOI":"10.1016\/j.jmb.2020.06.021","article-title":"Protofilament Structure and Supramolecular Polymorphism of Aggregated Mutant Huntingtin Exon 1","volume":"432","author":"Boatz","year":"2020","journal-title":"J. Mol. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/nchembio.1858","article-title":"Catalytic In Vivo Protein Knockdown by Small-Molecule PROTACs","volume":"11","author":"Bondeson","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.chembiol.2017.09.010","article-title":"Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead","volume":"25","author":"Bondeson","year":"2018","journal-title":"Cel Chem. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/mt.2008.231","article-title":"Artificial MicroRNAs as siRNA Shuttles: Improved Safety as Compared to shRNAs In Vitro and In Vivo","volume":"17","author":"Boudreau","year":"2009","journal-title":"Mol. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.ymthe.2004.05.024","article-title":"Recombinant AAV Viral Vectors Pseudotyped with Viral Capsids from Serotypes 1, 2, and 5 Display Differential Efficiency and Cell Tropism after Delivery to Different Regions of the Central Nervous System","volume":"10","author":"Burger","year":"2004","journal-title":"Mol. Ther."},{"key":"B17","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1093\/nar\/gkz976","article-title":"Potent and Sustained Huntingtin Lowering via AAV5 Encoding miRNA Preserves Striatal Volume and Cognitive Function in a Humanized Mouse Model of Huntington Disease","volume":"48","author":"Caron","year":"2020","journal-title":"Nucleic Ccids Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.1038\/mt.2011.201","article-title":"Potent and Selective Antisense Oligonucleotides Targeting Single-Nucleotide Polymorphisms in the Huntington Disease Gene\/Allele-specific Silencing of Mutant Huntingtin","volume":"19","author":"Carroll","year":"2011","journal-title":"Mol. Ther."},{"key":"B19","doi-asserted-by":"publisher","first-page":"11884","DOI":"10.1073\/pnas.182276099","article-title":"Huntington's Disease Age-Of-Onset Linked to Polyglutamine Aggregation Nucleation","volume":"99","author":"Chen","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B20","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1006\/jmbi.2001.4850","article-title":"Polyglutamine Aggregation Behavior In Vitro Supports a Recruitment Mechanism of Cytotoxicity","volume":"311","author":"Chen","year":"2001","journal-title":"J. Mol. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"16685","DOI":"10.1073\/pnas.0707842104","article-title":"A Small-Molecule Therapeutic lead for Huntington's Disease: Preclinical Pharmacology and Efficacy of C2-8 in the R6\/2 Transgenic Mouse","volume":"104","author":"Chopra","year":"2007","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1016\/j.cell.2017.10.033","article-title":"A Method for the Acute and Rapid Degradation of Endogenous Proteins","volume":"171","author":"Clift","year":"2017","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3678","DOI":"10.1242\/jcs.126086","article-title":"Transfer of Polyglutamine Aggregates in Neuronal Cells Occurs in Tunneling Nanotubes","volume":"126","author":"Costanzo","year":"2013","journal-title":"J. Cel Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1039\/c0mb00074d","article-title":"Impact of Linker Length on the Activity of PROTACs","volume":"7","author":"Cyrus","year":"2011","journal-title":"Mol. Biosyst."},{"key":"B25","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/s0092-8674(00)80513-9","article-title":"Formation of Neuronal Intranuclear Inclusions Underlies the Neurological Dysfunction in Mice Transgenic for the HD Mutation","volume":"90","author":"Davies","year":"1997","journal-title":"Cell"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.3390\/jcm9062004","article-title":"Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development","volume":"9","author":"Dhuri","year":"2020","journal-title":"Jcm"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1016\/j.celrep.2018.07.106","article-title":"Nuclear Localization of Huntingtin mRNA Is Specific to Cells of Neuronal Origin","volume":"24","author":"Didiot","year":"2018","journal-title":"Cel Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e1006846","DOI":"10.1371\/journal.pgen.1006846","article-title":"Elimination of Huntingtin in the Adult Mouse Leads to Progressive Behavioral Deficits, Bilateral Thalamic Calcification, and Altered Brain Iron Homeostasis","volume":"13","author":"Dietrich","year":"2017","journal-title":"Plos Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"17204","DOI":"10.1073\/pnas.0708285104","article-title":"Therapeutic Silencing of Mutant Huntingtin with siRNA Attenuates Striatal and Cortical Neuropathology and Behavioral Deficits","volume":"104","author":"DiFiglia","year":"2007","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.nbd.2018.08.019","article-title":"Mutational Analysis Implicates the Amyloid Fibril as the Toxic Entity in Huntington's Disease","volume":"120","author":"Drombosky","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e99341","DOI":"10.1371\/journal.pone.0099341","article-title":"Allele-Specific Silencing of Mutant Huntingtin in Rodent Brain and Human Stem Cells","volume":"9","author":"Drouet","year":"2014","journal-title":"PLoS ONE"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1016\/j.ymthe.2018.06.021","article-title":"AAV5-miHTT Gene Therapy Demonstrates Broad Distribution and Strong Human Mutant Huntingtin Lowering in a Huntington's Disease Minipig Model","volume":"26","author":"Evers","year":"2018","journal-title":"Mol. Ther."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e24308","DOI":"10.1371\/journal.pone.0024308","article-title":"Targeting Several CAG Expansion Diseases by a Single Antisense Oligonucleotide","volume":"6","author":"Evers","year":"2011","journal-title":"PLoS ONE"},{"key":"B34","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1089\/nat.2013.0452","article-title":"Preventing Formation of Toxic N-Terminal Huntingtin Fragments through Antisense Oligonucleotide-Mediated Protein Modification","volume":"24","author":"Evers","year":"2014","journal-title":"Nucleic Acid Ther."},{"key":"B35","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1038\/mt.2008.50","article-title":"AAV Vector-Mediated RNAi of Mutant Huntingtin Expression Is Neuroprotective in a Novel Genetic Rat Model of Huntington's Disease","volume":"16","author":"Franich","year":"2008","journal-title":"Mol. Ther."},{"key":"B36","doi-asserted-by":"publisher","first-page":"26188","DOI":"10.1074\/jbc.M710521200","article-title":"Heat Shock Transcription Factor 1-activating Compounds Suppress Polyglutamine-Induced Neurodegeneration through Induction of Multiple Molecular Chaperones","volume":"283","author":"Fujikake","year":"2008","journal-title":"J. Biol. Chem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"20211","DOI":"10.1074\/jbc.M401267200","article-title":"Inhibition of Calpain Cleavage of Huntingtin Reduces Toxicity","volume":"279","author":"Gafni","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"10166","DOI":"10.1021\/bi101208k","article-title":"Allele-Selective Inhibition of Mutant Huntingtin Expression with Antisense Oligonucleotides Targeting the Expanded CAG Repeat","volume":"49","author":"Gagnon","year":"2010","journal-title":"Biochemistry"},{"key":"B39","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1021\/acsmedchemlett.9b00597","article-title":"PROTAC Technology: Opportunities and Challenges","volume":"11","author":"Gao","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1016\/j.cell.2006.04.026","article-title":"Cleavage at the Caspase-6 Site Is Required for Neuronal Dysfunction and Degeneration Due to Mutant Huntingtin","volume":"125","author":"Graham","year":"2006","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nature04791","article-title":"Fatality in Mice Due to Oversaturation of Cellular microRNA\/short Hairpin RNA Pathways","volume":"441","author":"Grimm","year":"2006","journal-title":"Nature"},{"key":"B42","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/nature25502","article-title":"The Cryo-Electron Microscopy Structure of Huntingtin","volume":"555","author":"Guo","year":"2018","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.1073\/pnas.0501507102","article-title":"RNA Interference Improves Motor and Neuropathological Abnormalities in a Huntington's Disease Mouse Model","volume":"102","author":"Harper","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev.biochem.67.1.425","article-title":"The Ubiquitin System","volume":"67","author":"Hershko","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1089\/nat.2018.0775","article-title":"Lowering Mutant Huntingtin Using Tricyclo-DNA Antisense Oligonucleotides as a Therapeutic Approach for Huntington's Disease","volume":"29","author":"Imbert","year":"2019","journal-title":"Nucleic Acid Ther."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3579","DOI":"10.1021\/acs.biochem.7b00138.Formation","article-title":"Formation and Structure of Wild Type Huntingtin Exon-1 Fibrils","volume":"56","author":"Isas","year":"2017","journal-title":"Biochemistry"},{"key":"B47","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.1021\/ja100691p","article-title":"Protein Knockdown Using Methyl Bestatin\u2212Ligand Hybrid Molecules: Design and Synthesis of Inducers of Ubiquitination-Mediated Degradation of Cellular Retinoic Acid-Binding Proteins","volume":"132","author":"Itoh","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"B48","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s00401-016-1582-9","article-title":"Human-to-mouse Prion-like Propagation of Mutant Huntingtin Protein","volume":"132","author":"Jeon","year":"2016","journal-title":"Acta Neuropathol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1021\/acschembio.7b00985","article-title":"Development of Stabilized Peptide-Based PROTACs against Estrogen Receptor \u03b1","volume":"13","author":"Jiang","year":"2018","journal-title":"ACS Chem. Biol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"10141","DOI":"10.7150\/thno.46985","article-title":"The Peptide PROTAC Modality: A Novel Strategy for Targeted Protein Ubiquitination","volume":"10","author":"Jin","year":"2020","journal-title":"Theranostics"},{"key":"B51","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.molcel.2016.03.017","article-title":"The S\/T-Rich Motif in the DNAJB6 Chaperone Delays Polyglutamine Aggregation and the Onset of Disease in a Mouse Model","volume":"62","author":"Kakkar","year":"2016","journal-title":"Mol. Cel"},{"key":"B52","doi-asserted-by":"publisher","first-page":"3359","DOI":"10.1093\/hmg\/ddg352","article-title":"Dramatic Tissue-specific Mutation Length Increases Are an Early Molecular Event in Huntington Disease Pathogenesis","volume":"12","author":"Kennedy","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1093\/hmg\/9.17.2539","article-title":"Dramatic Mutation Instability in HD Mouse Striatum: Does Polyglutamine Load Contribute to Cell-specific Vulnerability in Huntington's Disease","volume":"9","author":"Kennedy","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-53410-z","article-title":"Discovery of a Potent Small Molecule Inhibiting Huntington's Disease (HD) Pathogenesis via Targeting CAG Repeats RNA and Poly Q Protein","volume":"9","author":"Khan","year":"2019","journal-title":"Sci. Rep."},{"key":"B55","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.molcel.2016.07.022","article-title":"Soluble Oligomers of PolyQ-Expanded Huntingtin Target a Multiplicity of Key Cellular Factors","volume":"63","author":"Kim","year":"2016","journal-title":"Mol. Cel"},{"key":"B56","doi-asserted-by":"publisher","first-page":"12784","DOI":"10.1073\/pnas.221451398","article-title":"Caspase 3-cleaved N-Terminal Fragments of Wild-type and Mutant Huntingtin Are Present in normal and Huntington's Disease Brains, Associate with Membranes, and Undergo Calpain-dependent Proteolysis","volume":"98","author":"Kim","year":"2001","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"18492","DOI":"10.1523\/JNEUROSCI.3219-11.2011","article-title":"Constitutive Upregulation of Chaperone-Mediated Autophagy in Huntington's Disease","volume":"31","author":"Koga","year":"2011","journal-title":"J. Neurosci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/j.neuron.2012.05.009","article-title":"Sustained Therapeutic Reversal of Huntington's Disease by Transient Repression of Huntingtin Synthesis","volume":"74","author":"Kordasiewicz","year":"2012","journal-title":"Neuron"},{"key":"B59","doi-asserted-by":"publisher","first-page":"8808","DOI":"10.1074\/jbc.M109.075028","article-title":"Proteolysis of Mutant Huntingtin Produces an Exon 1 Fragment that Accumulates as an Aggregated Protein in Neuronal Nuclei in huntington Disease","volume":"285","author":"Landles","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B60","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-019-1722-1","article-title":"Allele-selective Lowering of Mutant HTT Protein by HTT-LC3 Linker Compounds","volume":"575","author":"Li","year":"2019","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1021\/acscentsci.9b00467","article-title":"Enhancement of the Anti-aggregation Activity of a Molecular Chaperone Using a Rationally Designed Post-Translational Modification","volume":"5","author":"Lindstedt","year":"2019","journal-title":"ACS Cent. Sci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"293","DOI":"10.2183\/pjab.79B.293","article-title":"Specific Inhibition of Huntington's Disease Gene Expression by siRNAs in Cultured Cells","author":"Liu","year":"2003","journal-title":"Proc. Jpn. Acad. Ser. B: Phys. Biol. Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1021\/acschemneuro.0c00226","article-title":"Discovery of Small Molecule Inhibitors of Huntingtin Exon 1 Aggregation by FRET-Based High-Throughput Screening in Living Cells","volume":"11","author":"Lo","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/S1097-2765(02)00602-0","article-title":"Proteases Acting on Mutant Huntingtin Generate Cleaved Products that Differentially Build up Cytoplasmic and Nuclear Inclusions","volume":"10","author":"Lunkes","year":"2002","journal-title":"Mol. Cel"},{"key":"B65","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","article-title":"Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic Mice","volume":"87","author":"Mangiarini","year":"1996","journal-title":"Cell"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-25903-w","article-title":"A Human Huntingtin SNP Alters post-translational Modification and Pathogenic Proteolysis of the Protein Causing Huntington Disease","volume":"8","author":"Martin","year":"2018","journal-title":"Sci. Rep."},{"key":"B67","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1038\/mt.2011.219","article-title":"Preclinical Safety of RNAi-Mediated HTT Suppression in the Rhesus Macaque as a Potential Therapy for Huntington's Disease","volume":"19","author":"McBride","year":"2011","journal-title":"Mol. Ther."},{"key":"B68","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1111\/ene.13413","article-title":"Huntington's Disease: a Clinical Review","volume":"25","author":"McColgan","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"8173","DOI":"10.1002\/anie.201914751","article-title":"Systemic Brain Delivery of Antisense Oligonucleotides across the Blood-Brain Barrier with a Glucose\u2010Coated Polymeric Nanocarrier","volume":"59","author":"Min","year":"2020","journal-title":"Angew. Chem. Int. Ed."},{"key":"B70","doi-asserted-by":"publisher","first-page":"e297","DOI":"10.1038\/mtna.2016.7","article-title":"Design, Characterization, and Lead Selection of Therapeutic miRNAs Targeting Huntingtin for Development of Gene Therapy for Huntington's Disease","volume":"5","author":"Miniarikova","year":"2016","journal-title":"Mol. Ther. - Nucleic Acids"},{"key":"B71","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1074\/jbc.M114.603332","article-title":"Molecular Interaction between the Chaperone Hsc70 and the N-Terminal Flank of Huntingtin Exon 1 Modulates Aggregation","volume":"290","author":"Monsellier","year":"2015","journal-title":"J. Biol. Chem."},{"key":"B72","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/0092-8674(95)90542-1","article-title":"Targeted Disruption of the Huntington's Disease Gene Results in Embryonic Lethality and Behavioral and Morphological Changes in Heterozygotes","volume":"81","author":"Nasir","year":"1995","journal-title":"Cell"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-06281-3","article-title":"Regulatory Mechanisms of Incomplete Huntingtin mRNA Splicing","volume":"9","author":"Neueder","year":"2018","journal-title":"Nat. Commun."},{"key":"B74","doi-asserted-by":"publisher","first-page":"21807","DOI":"10.1074\/jbc.M109.084434","article-title":"Tracking Mutant Huntingtin Aggregation Kinetics in Cells Reveals Three Major Populations that Include an Invariant Oligomer Pool","volume":"285","author":"Olshina","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B75","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41598-020-74042-8","article-title":"Wild-type Huntingtin Regulates Human Macrophage Function","volume":"10","author":"O\u2019Regan","year":"2020","journal-title":"Sci. Rep."},{"key":"B76","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1089\/hum.2017.199","article-title":"Artificial miRNAs Reduce Human Mutant Huntingtin throughout the Striatum in a Transgenic Sheep Model of Huntington's Disease","volume":"29","author":"Pfister","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"B77","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.cub.2009.03.030.Five","article-title":"Five siRNAs Targeting Three SNPs May Provide Therapy for Three-Quarters of Huntington's Disease Patients","volume":"19","author":"Pfister","year":"2009","journal-title":"Curr. Biol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1158\/2159-8290.CD-NB2020-054","article-title":"Proof-of-Concept with PROTACs in Prostate Cancer","volume":"10","author":"Poh","year":"2020","journal-title":"Cancer Discov."},{"key":"B79","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/S0896-6273(03)00697-4","article-title":"A Rapid Cellular FRET Assay of Polyglutamine Aggregation Identifies a Novel Inhibitor","volume":"40","author":"Pollitt","year":"2003","journal-title":"Neuron"},{"key":"B80","doi-asserted-by":"publisher","first-page":"e46834","DOI":"10.1371\/journal.pone.0046834","article-title":"The Role of Chaperone-Mediated Autophagy in Huntingtin Degradation","volume":"7","author":"Qi","year":"2012","journal-title":"PLoS ONE"},{"key":"B81","doi-asserted-by":"publisher","first-page":"113091","DOI":"10.1016\/j.ejmech.2020.113091","article-title":"Discovery of Selective CDK9 Degraders with Enhancing Antiproliferative Activity through PROTAC Conversion","volume":"211","author":"Qiu","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"B82","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/j.celrep.2017.04.029","article-title":"Huntingtin Inclusions Trigger Cellular Quiescence, Deactivate Apoptosis, and Lead to Delayed Necrosis","volume":"19","author":"Ramdzan","year":"2017","journal-title":"Cel Rep."},{"key":"B83","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.4161\/cc.20423","article-title":"Huntingtin Protein Interactions Altered by Polyglutamine Expansion as Determined by Quantitative Proteomic Analysis","volume":"11","author":"Ratovitski","year":"2012","journal-title":"Cell Cycle"},{"key":"B84","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/ng1362","article-title":"Inhibition of mTOR Induces Autophagy and Reduces Toxicity of Polyglutamine Expansions in Fly and Mouse Models of Huntington Disease","volume":"36","author":"Ravikumar","year":"2004","journal-title":"Nat. Genet."},{"key":"B85","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/B978-0-12-381328-2.00014-6","article-title":"Genetics and Neuropathology of Huntington's Disease","volume":"98","author":"Reiner","year":"2011","journal-title":"Int. Rev. Neurobiol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nrneurol.2017.148","article-title":"Antisense Oligonucleotides: The Next Frontier for Treatment of Neurological Disorders","volume":"14","author":"Rinaldi","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-65046-5","article-title":"Co-chaperones DNAJA1 and DNAJB6 Are Critical for Regulation of Polyglutamine Aggregation","volume":"10","author":"Rodr\u00edguez-Gonz\u00e1lez","year":"2020","journal-title":"Sci. Rep."},{"key":"B88","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/j.ymthe.2005.05.006","article-title":"Intrastriatal rAAV-Mediated Delivery of Anti-huntingtin shRNAs Induces Partial Reversal of Disease Progression in R6\/1 Huntington's Disease Transgenic Mice","volume":"12","author":"Rodriguez-Lebron","year":"2005","journal-title":"Mol. Ther."},{"key":"B89","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1021\/jm980403y","article-title":"Structural Basis for Inhibition of the Hsp90 Molecular Chaperone by the Antitumor Antibiotics Radicicol and Geldanamycin","volume":"42","author":"Roe","year":"1999","journal-title":"J. Med. Chem."},{"key":"B90","doi-asserted-by":"publisher","first-page":"8554","DOI":"10.1073\/pnas.141230798","article-title":"Protacs: Chimeric Molecules that Target Proteins to the Skp1-Cullin-F Box Complex for Ubiquitination and Degradation","volume":"98","author":"Sakamoto","year":"2001","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.bbrc.2019.10.041","article-title":"Number and Molecular Brightness Analysis Reveals Htt25Q Protein Aggregation upon the Uptake of Htt97Q Aggregates","volume":"522","author":"Sameni","year":"2020","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B92","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1073\/pnas.1221891110\/-\/DCSupplemental","article-title":"Aberrant Splicing of HTT Generates the Pathogenic Exon 1 Protein in Huntington Disease","volume":"110","author":"Sathasivam","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B93","doi-asserted-by":"publisher","first-page":"4604","DOI":"10.1073\/pnas.96.8.4604","article-title":"Self-assembly of Polyglutamine-Containing Huntingtin Fragments into Amyloid-like Fibrils: Implications for Huntington's Disease pathologyMedical Sciences Communicated by Max F. Perutz","volume":"96","author":"Scherzinger","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B94","doi-asserted-by":"publisher","first-page":"5904","DOI":"10.1016\/j.bmcl.2008.07.114","article-title":"Targeted Intracellular Protein Degradation Induced by a Small Molecule: En Route to Chemical Proteomics","volume":"18","author":"Schneekloth","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B95","doi-asserted-by":"publisher","first-page":"3748","DOI":"10.1021\/ja039025z","article-title":"Chemical Genetic Control of Protein Levels: Selective In Vivo Targeted Degradation","volume":"126","author":"Schneekloth","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"B96","doi-asserted-by":"publisher","first-page":"282","DOI":"10.15252\/embj.201797212","article-title":"Complete Suppression of Htt Fibrilization and Disaggregation of Htt Fibrils by a Trimeric Chaperone Complex","volume":"37","author":"Scior","year":"2018","journal-title":"Embo J."},{"key":"B97","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/cdd.2012.72","article-title":"Ubiquitination and Selective Autophagy","volume":"20","author":"Shaid","year":"2013","journal-title":"Cell Death Differ"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1093\/hmg\/ddm054","article-title":"Triplet Repeat Mutation Length Gains Correlate with Cell-type Specific Vulnerability in Huntington Disease Brain","volume":"16","author":"Shelbourne","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"B99","doi-asserted-by":"publisher","first-page":"14367","DOI":"10.1073\/pnas.0602348103","article-title":"Normal-repeat-length Polyglutamine Peptides Accelerate Aggregation Nucleation and Cytotoxicity of Expanded Polyglutamine Proteins","volume":"103","author":"Slepko","year":"2006","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1002\/jnr.24505.Circadian","article-title":"Circadian Dysfunction in the Q175 Model of Huntington's Disease: Network Analysis","volume":"97","author":"Smarr","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-08027-7","article-title":"Differential PROTAC Substrate Specificity Dictated by Orientation of Recruited E3 Ligase","volume":"10","author":"Smith","year":"2019","journal-title":"Nat. Commun."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/scitranslmed.aar3959","article-title":"Huntingtin Suppression Restores Cognitive Function in a Mouse Model of Huntington's Disease","volume":"10","author":"Southwell","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"B103","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1038\/mt.2014.153","article-title":"In Vivo Evaluation of Candidate Allele-specific Mutant Huntingtin Gene Silencing Antisense Oligonucleotides","volume":"22","author":"Southwell","year":"2014","journal-title":"Mol. Ther."},{"key":"B104","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.omtm.2019.03.002","article-title":"AAV5-miHTT Gene Therapy Demonstrates Sustained Huntingtin Lowering and Functional Improvement in Huntington Disease Mouse Models","volume":"13","author":"Spronck","year":"2019","journal-title":"Mol. Ther. - Methods Clin. Develop."},{"key":"B105","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1089\/hum.2013.200","article-title":"Silencing Mutant Huntingtin by Adeno-Associated Virus-Mediated RNA Interference Ameliorates Disease Manifestations in the YAC128 Mouse Model of Huntington's Disease","volume":"25","author":"Stanek","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"B106","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41392-019-0101-6","article-title":"Protacs: Great Opportunities for Academia and Industry","volume":"4","author":"Sun","year":"2019","journal-title":"Sig Transduct Target. Ther."},{"key":"B107","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/s0896-6273(03)00569-5","article-title":"Neuropathogenic Forms of Huntingtin and Androgen Receptor Inhibit Fast Axonal Transport","volume":"40","author":"Szebenyi","year":"2003","journal-title":"Neuron"},{"key":"B108","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1056\/NEJMoa1900907","article-title":"Targeting Huntingtin Expression in Patients with Huntington's Disease","volume":"380","author":"Tabrizi","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B109","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.molcel.2019.09.009","article-title":"AUTACs: Cargo-specific Degraders Using Selective Autophagy","volume":"76","author":"Takahashi","year":"2019","journal-title":"Mol. Cel"},{"key":"B110","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1093\/hmg\/ddm320","article-title":"Lysine 63-linked Ubiquitination Promotes the Formation and Autophagic Clearance of Protein Inclusions Associated with Neurodegenerative Diseases","volume":"17","author":"Tan","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"B111","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1038\/mp.2015.81","article-title":"Huntington's Disease Cerebrospinal Fluid Seeds Aggregation of Mutant Huntingtin","volume":"20","author":"Tan","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"B112","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1016\/j.str.2019.08.003.Structure","article-title":"Structure of Membrane-Bound Huntingtin Exon 1 Reveals Membrane Interaction and Aggregation Mechanisms","volume":"27","author":"Tao","year":"2019","journal-title":"Structure"},{"key":"B113","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nsmb.1570.Polyglutamine","article-title":"Polyglutamine Disruption of the Huntingtin Exon 1 N Terminus Triggers a Complex Aggregation Mechanism","volume":"16","author":"Thakur","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1083\/jcb.200909067","article-title":"IKK Phosphorylates Huntingtin and Targets it for Degradation by the Proteasome and Lysosome","volume":"187","author":"Thompson","year":"2009","journal-title":"J. Cel Biol."},{"key":"B115","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15252\/embj.2019103954","article-title":"The HSP110\/HSP70 Disaggregation System Generates Spreading\u2010competent Toxic \u03b1\u2010synuclein Species","volume":"39","author":"Tittelmeier","year":"2020","journal-title":"Embo J."},{"key":"B116","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.bmcl.2018.01.012","article-title":"Degradation of Huntingtin Mediated by a Hybrid Molecule Composed of IAP Antagonist Linked to Phenyldiazenyl Benzothiazole Derivative","volume":"28","author":"Tomoshige","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B117","doi-asserted-by":"publisher","first-page":"11530","DOI":"10.1002\/anie.201706529","article-title":"Discovery of Small Molecules that Induce the Degradation of Huntingtin","volume":"56","author":"Tomoshige","year":"2017","journal-title":"Angew. Chem. Int. Ed."},{"key":"B118","doi-asserted-by":"publisher","first-page":"e0212337","DOI":"10.1371\/journal.pone.0212337","article-title":"Huntingtin Associates with the Actin Cytoskeleton and \u03b1-actinin Isoforms to Influence Stimulus Dependent Morphology Changes","volume":"14","author":"Tousley","year":"2019","journal-title":"PLoS ONE"},{"key":"B119","doi-asserted-by":"publisher","first-page":"9000","DOI":"10.1523\/JNEUROSCI.0118-17.2017","article-title":"Mutant Huntingtin Is Secreted via a Late Endosomal\/lysosomal Unconventional Secretory Pathway","volume":"37","author":"Trajkovic","year":"2017","journal-title":"J. Neurosci."},{"key":"B120","doi-asserted-by":"publisher","first-page":"273","DOI":"10.37349\/etat.2020.00018","article-title":"Current Strategies for the Design of PROTAC Linkers: a Critical Review","volume":"1","author":"Troup","year":"2020","journal-title":"Exploration Targeted Anti-Tumor Ther."},{"key":"B121","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.str.2020.04.008","article-title":"Flanking Regions Determine the Structure of the Poly-Glutamine in Huntingtin through Mechanisms Common Among Glutamine-Rich Human Proteins","volume":"28","author":"Urbanek","year":"2020","journal-title":"Structure"},{"key":"B122","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/S1474-4422(09)70178-4","article-title":"Beyond the Brain: Widespread Pathology in Huntington's Disease","volume":"8","author":"van der Burg","year":"2009","journal-title":"Lancet Neurol."},{"key":"B123","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1016\/j.jmb.2018.03.017","article-title":"Self-assembly of Mutant Huntingtin Exon-1 Fragments into Large Complex Fibrillar Structures Involves Nucleated Branching","volume":"430","author":"Wagner","year":"2018","journal-title":"J. Mol. Biol."},{"key":"B124","doi-asserted-by":"publisher","first-page":"3359","DOI":"10.1073\/pnas.1524575113","article-title":"Ablation of Huntingtin in Adult Neurons Is Nondeleterious but its Depletion in Young Mice Causes Acute Pancreatitis","volume":"113","author":"Wang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B125","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.neures.2005.06.021","article-title":"Clinico-pathological rescue of a Model Mouse of Huntington's Disease by siRNA","volume":"53","author":"Wang","year":"2005","journal-title":"Neurosci. Res."},{"key":"B126","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.ajhg.2009.02.003","article-title":"CAG Expansion in the Huntington Disease Gene Is Associated with a Specific and Targetable Predisposing Haplogroup","volume":"84","author":"Warby","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"B127","doi-asserted-by":"publisher","first-page":"112903","DOI":"10.1016\/j.ejmech.2020.112903","article-title":"First Orally Bioavailable Prodrug of Proteolysis Targeting Chimera (PROTAC) Degrades Cyclin-dependent Kinases 2\/4\/6 In Vivo","volume":"209","author":"Wei","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"B128","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1126\/science.aab1433","article-title":"Phthalimide Conjugation as a Strategy for In Vivo Target Protein Degradation","volume":"348","author":"Winter","year":"2015","journal-title":"Science"},{"key":"B129","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1038\/aps.2016.31","article-title":"A High-Throughput-Compatible Assay to Measure the Degradation of Endogenous Huntingtin Proteins","volume":"37","author":"Wu","year":"2016","journal-title":"Acta Pharmacol. Sin"},{"key":"B130","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep34916","article-title":"Multiple Discrete Soluble Aggregates Influence Polyglutamine Toxicity in a Huntington's Disease Model System","volume":"6","author":"Xi","year":"2016","journal-title":"Sci. Rep."},{"key":"B131","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.mcn.2015.01.003","article-title":"Chaperone Mediated Autophagy to the rescue: A New-Fangled Target for the Treatment of Neurodegenerative Diseases","volume":"66","author":"Xilouri","year":"2015","journal-title":"Mol. Cell Neurosci."},{"key":"B132","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S0092-8674(00)80623-6","article-title":"Reversal of Neuropathology and Motor Dysfunction in a Conditional Model of Huntington's Disease","volume":"101","author":"Yamamoto","year":"2000","journal-title":"Cell"},{"key":"B133","doi-asserted-by":"publisher","first-page":"115175","DOI":"10.1016\/j.bmc.2019.115175","article-title":"Application of Protein Knockdown Strategy Targeting \u03b2-sheet Structure to Multiple Disease-Associated Polyglutamine Proteins","volume":"28","author":"Yamashita","year":"2020","journal-title":"Bioorg. Med. Chem."},{"key":"B134","doi-asserted-by":"publisher","first-page":"113150","DOI":"10.1016\/j.ejmech.2020.113150","article-title":"Discovery of a PROTAC Targeting ALK with In Vivo Activity","volume":"212","author":"Yan","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"B135","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-16318-1","article-title":"Truncation of Mutant Huntingtin in Knock-In Mice Demonstrates Exon1 Huntingtin Is a Key Pathogenic Form","volume":"11","author":"Yang","year":"2020","journal-title":"Nat. Commun."},{"key":"B136","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1021\/acschembio.5b00216","article-title":"Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4","volume":"10","author":"Zengerle","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"B137","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1073\/pnas.0408936102","article-title":"A Potent Small Molecule Inhibits Polyglutamine Aggregation in Huntington's Disease Neurons and Suppresses Neurodegeneration In Vivo","volume":"102","author":"Zhang","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B138","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1111\/j.1471-4159.2008.05734.x","article-title":"Allele-specific Silencing of Mutant Huntington's Disease Gene","volume":"108","author":"Zhang","year":"2009","journal-title":"J. Neurochem."},{"key":"B139","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/ng1219","article-title":"Huntingtin Interacts with REST\/NRSF to Modulate the Transcription of NRSE-Controlled Neuronal Genes","volume":"35","author":"Zuccato","year":"2003","journal-title":"Nat. Genet."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2021.769184\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T06:35:24Z","timestamp":1636698924000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2021.769184\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,12]]},"references-count":139,"alternative-id":["10.3389\/fmolb.2021.769184"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2021.769184","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,12]]},"article-number":"769184"}}