{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:37:06Z","timestamp":1791175026477,"version":"4.1.0"},"reference-count":50,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,4,1]]},"abstract":"<jats:p>HD (Huntington's disease) is produced by the expression of mutant forms of the protein htt (huntingtin) containing a pathologically expanded poly-glutamine repeat. For unknown reasons, in HD patients and HD mouse models, neurons from the striatum and cerebral cortex degenerate and lead to motor dysfunction and dementia. Synaptic transmission in those neurons becomes progressively altered during the course of the disease. However, the relationship between synaptic dysfunction and neurodegeneration in HD is not yet clear. Are there early specific functional synaptic changes preceding symptoms and neurodegeneration? What is the role of those changes in neuronal damage? Recent experiments in a Drosophila model of HD have showed that abnormally increased neurotransmitter release might be a leading cause of neurodegeneration. In the present review, we summarize recently described synaptic alterations in HD animal models and discuss potential underlying molecular mechanisms.<\/jats:p>","DOI":"10.1042\/bst0380488","type":"journal-article","created":{"date-parts":[[2010,3,24]],"date-time":"2010-03-24T14:16:27Z","timestamp":1269440187000},"page":"488-492","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Presynaptic dysfunction in Huntington's disease"],"prefix":"10.1042","volume":"38","author":[{"given":"Jos\u00e9\u00a0L.","family":"Rozas","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hosp. Univ. Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, Dpto. de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica Universidad de Sevilla, Avda. S\u00e1nchez-Pizju\u00e1n 4, 41009 Sevilla, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"G\u00f3mez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hosp. Univ. Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, Dpto. de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica Universidad de Sevilla, Avda. S\u00e1nchez-Pizju\u00e1n 4, 41009 Sevilla, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Tom\u00e1s-Zapico","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, CSIC\/UAM, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9\u00a0J.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa, CSIC\/UAM, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Fern\u00e1ndez-Chac\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hosp. Univ. Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, Dpto. de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica Universidad de Sevilla, Avda. S\u00e1nchez-Pizju\u00e1n 4, 41009 Sevilla, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2010,3,22]]},"reference":[{"key":"2021111720550022100_B1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes","volume":"72","author":"The Huntington's Disease Collaborative Research Group","year":"1993","journal-title":"Cell"},{"key":"2021111720550022100_B2","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.bbadis.2009.04.001","article-title":"Mouse models of Huntington's disease and methodological considerations for therapeutic trials","volume":"1792","author":"Ferrante","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"2021111720550022100_B3","doi-asserted-by":"crossref","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":"2021111720550022100_B4","doi-asserted-by":"crossref","first-page":"9361","DOI":"10.1523\/JNEUROSCI.2365-04.2004","article-title":"Biochemical, ultrastructural, and reversibility studies on huntingtin filaments isolated from mouse and human brain","volume":"24","author":"Diaz-Hernandez","year":"2004","journal-title":"J. Neurosci."},{"key":"2021111720550022100_B5","doi-asserted-by":"crossref","first-page":"9773","DOI":"10.1523\/JNEUROSCI.3183-05.2005","article-title":"Full motor recovery despite striatal neuron loss and formation of irreversible amyloid-like inclusions in a conditional mouse model of Huntington's disease","volume":"25","author":"Diaz-Hernandez","year":"2005","journal-title":"J. Neurosci."},{"key":"2021111720550022100_B6","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1073\/pnas.96.1.179","article-title":"Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron","volume":"96","author":"Faber","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111720550022100_B7","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S0896-6273(00)80573-5","article-title":"Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons","volume":"21","author":"Jackson","year":"1998","journal-title":"Neuron"},{"key":"2021111720550022100_B8","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1073\/pnas.0400243101","article-title":"Cytoplasmic aggregates trap polyglutamine-containing proteins and block axonal transport in a Drosophila model of Huntington's disease","volume":"101","author":"Lee","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111720550022100_B9","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1126\/science.1072613","article-title":"Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease","volume":"296","author":"Dunah","year":"2002","journal-title":"Science"},{"key":"2021111720550022100_B10","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1007\/s00018-007-7222-8","article-title":"Is the ubiquitin\u2013proteasome system impaired in Huntington's disease?","volume":"64","author":"Ortega","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"key":"2021111720550022100_B11","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1093\/hmg\/ddl434","article-title":"Mutant huntingtin inhibits clathrin-independent endocytosis and causes accumulation of cholesterol in vitro and in vivo","volume":"15","author":"Trushina","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"2021111720550022100_B12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0896-6273(03)00594-4","article-title":"Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila","volume":"40","author":"Gunawardena","year":"2003","journal-title":"Neuron"},{"key":"2021111720550022100_B13","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/nn.2346","article-title":"Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin","volume":"12","author":"Morfini","year":"2009","journal-title":"Nat. Neurosci."},{"key":"2021111720550022100_B14","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.cell.2004.06.018","article-title":"Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules","volume":"118","author":"Gauthier","year":"2004","journal-title":"Cell"},{"key":"2021111720550022100_B15","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1523\/JNEUROSCI.4411-08.2009","article-title":"Neuroprotective effects of inositol 1,4,5-trisphosphate receptor C-terminal fragment in a Huntington's disease mouse model","volume":"29","author":"Tang","year":"2009","journal-title":"J. Neurosci."},{"key":"2021111720550022100_B16","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0896-6273(03)00366-0","article-title":"Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type\u00a01","volume":"39","author":"Tang","year":"2003","journal-title":"Neuron"},{"key":"2021111720550022100_B17","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1111\/j.1460-9568.2004.03633.x","article-title":"HAP1 facilitates effects of mutant huntingtin on inositol 1,4,5-trisphosphate-induced Ca release in primary culture of striatal medium spiny neurons","volume":"20","author":"Tang","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"2021111720550022100_B18","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1007\/s00018-005-5084-5","article-title":"Synaptic dysfunction in Huntington's disease: a new perspective","volume":"62","author":"Smith","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"2021111720550022100_B19","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0896-6273(02)00615-3","article-title":"Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease","volume":"33","author":"Zeron","year":"2002","journal-title":"Neuron"},{"key":"2021111720550022100_B20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.neuron.2007.11.025","article-title":"Suppression of neurodegeneration and increased neurotransmission caused by expanded full-length huntingtin accumulating in the cytoplasm","volume":"57","author":"Romero","year":"2008","journal-title":"Neuron"},{"key":"2021111720550022100_B21","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.mcn.2005.07.016","article-title":"Crosstalk between huntingtin and syntaxin 1A regulates N-type calcium channels","volume":"30","author":"Swayne","year":"2005","journal-title":"Mol. Cell Neurosci."},{"key":"2021111720550022100_B22","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.1073\/pnas.0409402102","article-title":"Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease","volume":"102","author":"Tang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111720550022100_B23","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1096\/fj.08-122275","article-title":"Altered P2X7-receptor level and function in mouse models of Huntington's disease and therapeutic efficacy of antagonist administration","volume":"23","author":"Diaz-Hernandez","year":"2009","journal-title":"FASEB J."},{"key":"2021111720550022100_B24","doi-asserted-by":"crossref","first-page":"53072","DOI":"10.1074\/jbc.M306230200","article-title":"Cysteine string protein (CSP) inhibition of N-type calcium channels is blocked by mutant huntingtin","volume":"278","author":"Miller","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021111720550022100_B25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0896-6273(04)00190-4","article-title":"The synaptic vesicle protein CSP\u03b1 prevents presynaptic degeneration","volume":"42","author":"Fern\u00e1ndez-Chac\u00f3n","year":"2004","journal-title":"Neuron"},{"key":"2021111720550022100_B26","doi-asserted-by":"crossref","first-page":"10371","DOI":"10.1523\/JNEUROSCI.1592-09.2009","article-title":"Alterations in cortical excitation and inhibition in genetic mouse models of Huntington's disease","volume":"29","author":"Cummings","year":"2009","journal-title":"J. Neurosci."},{"key":"2021111720550022100_B27","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1523\/JNEUROSCI.23-03-00961.2003","article-title":"Transient and progressive electrophysiological alterations in the corticostriatal pathway in a mouse model of Huntington's disease","volume":"23","author":"Cepeda","year":"2003","journal-title":"J. Neurosci."},{"key":"2021111720550022100_B28","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1002\/jnr.20344","article-title":"Increased GABAergic function in mouse models of Huntington's disease: reversal by BDNF","volume":"78","author":"Cepeda","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"2021111720550022100_B29","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.nbd.2005.05.008","article-title":"Depletion of rabphilin 3A in a transgenic mouse model (R6\/1) of Huntington's disease, a possible culprit in synaptic dysfunction","volume":"20","author":"Smith","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"2021111720550022100_B30","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1471-4159.2007.04703.x","article-title":"Loss of SNAP-25 and rabphilin 3a in sensory-motor cortex in Huntington's disease","volume":"103","author":"Smith","year":"2007","journal-title":"J. Neurochem."},{"key":"2021111720550022100_B31","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1038\/sj.emboj.7601165","article-title":"Rabphilin regulates SNAREdependent re-priming of synaptic vesicles for fusion","volume":"25","author":"Deak","year":"2006","journal-title":"EMBO J."},{"key":"2021111720550022100_B32","doi-asserted-by":"crossref","first-page":"7941","DOI":"10.1523\/JNEUROSCI.20-21-07941.2000","article-title":"Novel SCAMPs lacking NPF repeats: ubiquitous and synaptic vesicle-specific forms implicate SCAMPs in multiple membrane-trafficking functions","volume":"20","author":"Fern\u00e1ndez-Chac\u00f3n","year":"2000","journal-title":"J. Neurosci."},{"key":"2021111720550022100_B33","doi-asserted-by":"crossref","first-page":"11318","DOI":"10.1074\/jbc.M807620200","article-title":"SCAMP5 links endoplasmic reticulum stress to the accumulation of expanded polyglutamine protein aggregates via endocytosis inhibition","volume":"284","author":"Noh","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021111720550022100_B34","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1093\/emboj\/cdg334","article-title":"Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking","volume":"22","author":"Metzler","year":"2003","journal-title":"EMBO J."},{"key":"2021111720550022100_B35","doi-asserted-by":"crossref","first-page":"11056","DOI":"10.1523\/JNEUROSCI.1941-07.2007","article-title":"Huntingtin-interacting protein 1 influences worm and mouse presynaptic function and protects Caenorhabditis elegans neurons against mutant polyglutamine toxicity","volume":"27","author":"Parker","year":"2007","journal-title":"J. Neurosci."},{"key":"2021111720550022100_B36","doi-asserted-by":"crossref","first-page":"11399","DOI":"10.1073\/pnas.0600784103","article-title":"Factors regulating the abundance and localization of synaptobrevin in the plasma membrane","volume":"103","author":"Dittman","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111720550022100_B37","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1385\/JMN:23:1-2:061","article-title":"Genetic and pharmacological suppression of polyglutamine-dependent neuronal dysfunction in Caenorhabditis elegans","volume":"23","author":"Parker","year":"2004","journal-title":"J. Mol. Neurosci."},{"key":"2021111720550022100_B38","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.neuron.2004.11.027","article-title":"Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins","volume":"44","author":"Huang","year":"2004","journal-title":"Neuron"},{"key":"2021111720550022100_B39","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1083\/jcb.200710061","article-title":"Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles","volume":"179","author":"Ohyama","year":"2007","journal-title":"J. Cell Biol."},{"key":"2021111720550022100_B40","doi-asserted-by":"crossref","first-page":"12874","DOI":"10.1523\/JNEUROSCI.2464-07.2007","article-title":"Drosophila huntingtin-interacting protein 14 is a presynaptic protein required for photoreceptor synaptic transmission and expression of the palmitoylated proteins synaptosome-associated protein 25 and cysteine string protein","volume":"27","author":"Stowers","year":"2007","journal-title":"J. Neurosci."},{"key":"2021111720550022100_B41","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.cell.2005.09.028","article-title":"\u03b1-Synuclein cooperates with CSP\u03b1 in preventing neurodegeneration","volume":"123","author":"Chandra","year":"2005","journal-title":"Cell"},{"key":"2021111720550022100_B42","doi-asserted-by":"crossref","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":"2021111720550022100_B43","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/502","article-title":"Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1","volume":"19","author":"Cummings","year":"1998","journal-title":"Nat. Genet."},{"key":"2021111720550022100_B44","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1126\/science.292.5521.1552","article-title":"Impairment of the ubiquitin\u2013proteasome system by protein aggregation","volume":"292","author":"Bence","year":"2001","journal-title":"Science"},{"key":"2021111720550022100_B45","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1111\/j.1471-4159.2006.03968.x","article-title":"Inhibition of 26S proteasome activity by huntingtin filaments but not inclusion bodies isolated from mouse and human brain","volume":"98","author":"Diaz-Hernandez","year":"2006","journal-title":"J. Neurochem."},{"key":"2021111720550022100_B46","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nature06022","article-title":"Global changes to the ubiquitin system in Huntington's disease","volume":"448","author":"Bennett","year":"2007","journal-title":"Nature"},{"key":"2021111720550022100_B47","doi-asserted-by":"crossref","first-page":"e5128","DOI":"10.1371\/journal.pone.0005128","article-title":"The ubiquitin-proteasome reporter GFPu does not accumulate in neurons of the R6\/2 transgenic mouse model of Huntington's disease","volume":"4","author":"Bett","year":"2009","journal-title":"PLoS ONE"},{"key":"2021111720550022100_B48","doi-asserted-by":"crossref","first-page":"13986","DOI":"10.1073\/pnas.0906463106","article-title":"Accumulation of ubiquitin conjugates in a polyglutamine disease model occurs without global ubiquitin\/proteasome system impairment","volume":"106","author":"Maynard","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111720550022100_B49","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1083\/jcb.200709080","article-title":"Impaired ubiquitin\u2013proteasome system activity in the synapses of Huntington's disease mice","volume":"180","author":"Wang","year":"2008","journal-title":"J. Cell Biol."},{"key":"2021111720550022100_B50","doi-asserted-by":"crossref","first-page":"11333","DOI":"10.1523\/JNEUROSCI.1684-06.2006","article-title":"Proteasome inhibition triggers activity-dependent increase in the size of the recycling vesicle pool in cultured hippocampal neurons","volume":"26","author":"Willeumier","year":"2006","journal-title":"J. Neurosci."}],"container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/38\/2\/488\/517250\/bst0380488.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/38\/2\/488\/517250\/bst0380488.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T09:01:20Z","timestamp":1711357280000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/38\/2\/488\/67166\/Presynaptic-dysfunction-in-Huntington-s-disease"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,22]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2010,3,22]]},"published-print":{"date-parts":[[2010,4,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bst0380488","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,22]]}}}