{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:48:22Z","timestamp":1790696902570,"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":[[2015,4,1]]},"abstract":"<jats:p>Microtubules (MTs) are dynamic polymers consisting of \u03b1\/\u03b2 tubulin dimers and playing a plethora of roles in eukaryotic cells. Looking at neurons, they are key determinants of neuronal polarity, axonal transport and synaptic plasticity. The concept that MT dysfunction can participate in, and perhaps lead to, Parkinson's disease (PD) progression has been suggested by studies using toxin-based and genetic experimental models of the disease. Here, we first learn lessons from MPTP and rotenone as well as from the PD related genes, including SNCA and LRRK2, and then look at old and new evidence regarding the interplay between parkin and MTs. Data from experimental models and human cells point out that parkin regulates MT stability and strengthen the link between MTs and PD paving the way to a viable strategy for the management of the disease.<\/jats:p>","DOI":"10.1042\/bst20150007","type":"journal-article","created":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T16:51:05Z","timestamp":1439311865000},"page":"292-296","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Linking microtubules to Parkinson's disease: the case of parkin"],"prefix":"10.1042","volume":"43","author":[{"given":"Graziella","family":"Cappelletti","sequence":"first","affiliation":[{"name":"Department of Biosciences, Universit\u00e0 degli Studi di Milano, I-20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Casagrande","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Universit\u00e0 degli Studi di Milano, I-20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Calogero","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Universit\u00e0 degli Studi di Milano, I-20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelita","family":"De Gregorio","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Universit\u00e0 degli Studi di Milano, I-20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Pezzoli","sequence":"additional","affiliation":[{"name":"Parkinson Institute, Istituti Clinici di Perfezionamento, I-20125 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Cartelli","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Universit\u00e0 degli Studi di Milano, I-20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2015,4,7]]},"reference":[{"key":"2021111720333250200_B1","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson's disease: mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"2021111720333250200_B2","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1038\/nm.2165","article-title":"Missing pieces in the Parkinson's disease puzzle","volume":"16","author":"Obeso","year":"2010","journal-title":"Nat. Med."},{"key":"2021111720333250200_B3","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S0140-6736(14)61010-2","article-title":"Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapeutic perspectives","volume":"384","author":"Shapira","year":"2014","journal-title":"Lancet"},{"key":"2021111720333250200_B4","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.cell.2009.12.011","article-title":"Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance","volume":"140","author":"Tischfield","year":"2010","journal-title":"Cell"},{"key":"2021111720333250200_B5","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.neuron.2014.09.027","article-title":"Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS","volume":"84","author":"Smith","year":"2014","journal-title":"Neuron"},{"key":"2021111720333250200_B6","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/S1474-4422(13)70090-5","article-title":"Tau pathology and neurodegeneration","volume":"12","author":"Spillantini","year":"2013","journal-title":"Lancet Neurol"},{"key":"2021111720333250200_B7","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.cell.2010.10.014","article-title":"A family of protein-deglutamylating enzymes associated with neurodegeneration","volume":"143","author":"Rogowski","year":"2010","journal-title":"Cell"},{"key":"2021111720333250200_B8","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/nrn3380","article-title":"Axonal transport deficits and neurodegenerative diseases","volume":"14","author":"Millecamps","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"2021111720333250200_B9","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.expneurol.2012.01.011","article-title":"Axon degeneration in Parkinson's disease","volume":"246","author":"Burke","year":"2013","journal-title":"Exp. Neurol."},{"key":"2021111720333250200_B10","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/312237a0","article-title":"Dynamic instability of microtubules growth","volume":"312","author":"Mitchison","year":"1984","journal-title":"Nature"},{"key":"2021111720333250200_B11","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/nrm3227","article-title":"Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions","volume":"12","author":"Janke","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021111720333250200_B12","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/nrn2631","article-title":"Microtubule assembly, organization and dynamics in axons and dendrites","volume":"10","author":"Conde","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"2021111720333250200_B13","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.neuron.2008.11.013","article-title":"Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity","volume":"61","author":"Jaworski","year":"2009","journal-title":"Neuron"},{"key":"2021111720333250200_B14","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.neuron.2013.01.036","article-title":"Transglutaminase and polyamination of tubulin: posttranslational modification for stabilizing axonal microtubules","volume":"78","author":"Song","year":"2013","journal-title":"Neuron"},{"key":"2021111720333250200_B15","doi-asserted-by":"publisher","first-page":"3139","DOI":"10.1007\/s00018-014-1610-7","article-title":"Transport and diffusion of Tau protein in neurons","volume":"71","author":"Scholz","year":"2014","journal-title":"Cell Mol. Life Sci."},{"key":"2021111720333250200_B16","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1111\/jnc.12621","article-title":"Microtubules in neurons as information carriers","volume":"129","author":"Dent","year":"2014","journal-title":"J. Neurochem."},{"key":"2021111720333250200_B17","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1600-0854.2008.00869.x","article-title":"Touch, grasp, deliver and control: functional cross-talk between microtubules and cell adhesions","volume":"10","author":"Akhmanova","year":"2009","journal-title":"Traffic (Copenhagen, Denmark)"},{"key":"2021111720333250200_B18","doi-asserted-by":"publisher","first-page":"4781","DOI":"10.1016\/j.febslet.2005.07.058","article-title":"The parkinsonism producing neurotoxin MPP+ affects microtubule dynamics by acting as a destabilising factor","volume":"579","author":"Cappelletti","year":"2005","journal-title":"FEBS Lett."},{"key":"2021111720333250200_B19","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1111\/j.1471-4159.2010.06924.x","article-title":"Microtubule dysfunction precedes transport impairment and mitochondria damage in MPP+-induced neurodegeneration","volume":"115","author":"Cartelli","year":"2010","journal-title":"J. Neurochem."},{"key":"2021111720333250200_B20","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1038\/srep01837","article-title":"Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer epothilone D is neuroprotective","volume":"3","author":"Cartelli","year":"2013","journal-title":"Sci. Rep."},{"key":"2021111720333250200_B21","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/0304-4165(78)90315-X","article-title":"Rotenone inhibition of tubulin self-assembly","volume":"543","author":"Marshall","year":"1978","journal-title":"Biochim. Biophys. Acta"},{"key":"2021111720333250200_B22","doi-asserted-by":"publisher","first-page":"34105","DOI":"10.1074\/jbc.M503483200","article-title":"Selectively vulnerability of dopaminergic neurons to microtubule depolymerization","volume":"280","author":"Ren","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2021111720333250200_B23","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1083\/jcb.201009132","article-title":"Loss of mitochondrial complex I activity potentiates dopamine neuron death induced by microtubule dysfunction in a Parkinson's disease model","volume":"192","author":"Choi","year":"2011","journal-title":"J. Cell Biol."},{"key":"2021111720333250200_B24","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/S0140-6736(10)62345-8","article-title":"Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies","volume":"377","author":"Nalls","year":"2011","journal-title":"Lancet"},{"key":"2021111720333250200_B25","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the alpha-synuclein gene identified in families with Parkinson's disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"key":"2021111720333250200_B26","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.1074\/jbc.M102981200","article-title":"Tubulin seeds alpha-synuclein fibril formation","volume":"277","author":"Alim","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2021111720333250200_B27","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3233\/JAD-2004-6412","article-title":"Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein","volume":"6","author":"Alim","year":"2004","journal-title":"J. Alzheimers Dis."},{"key":"2021111720333250200_B28","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1111\/j.1460-9568.2007.05757.x","article-title":"Regulation of the norepinephrine transporter by alpha-synuclein-mediated interactions with microtubules","volume":"26","author":"Jeannotte","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"2021111720333250200_B29","doi-asserted-by":"publisher","first-page":"21742","DOI":"10.1074\/jbc.M113.451815","article-title":"\u03b1-Synuclein oligomers impair neuronal microtubule-kinesin interplay","volume":"288","author":"Prots","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2021111720333250200_B30","doi-asserted-by":"publisher","first-page":"e94259","DOI":"10.1371\/journal.pone.0094259","article-title":"Extracellular \u03b1-synuclein leads to microtubule destabilization via GSK-3\u03b2-dependent Tau phosphorylation in PC12 cells","volume":"9","author":"Gassowska","year":"2014","journal-title":"PLoS One"},{"key":"2021111720333250200_B31","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.1111\/j.1471-4159.2009.06235.x","article-title":"Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoform and modulates microtubule stability: a point of convergence in parkinsonian neurodegeneration?","volume":"110","author":"Gillardon","year":"2009","journal-title":"J. Neurochem."},{"key":"2021111720333250200_B32","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1074\/jbc.M113.507913","article-title":"A direct interaction between leucine-rich repeat kinase 2 and specific \u03b2-tubulin isoforms regulates tubulin acetylation","volume":"289","author":"Law","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2021111720333250200_B33","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.neurobiolaging.2012.04.008","article-title":"DJ-1 deficiency perturbs microtubule dynamics and impairs striatal neurite outgrowth","volume":"34","author":"Sheng","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"2021111720333250200_B34","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/neuro.24.005.2009","article-title":"Microtubule depolymerisation potentiates alpha-synuclein oligomerization","volume":"1","author":"Esteves","year":"2010","journal-title":"Front. Aging Neurosci."},{"key":"2021111720333250200_B35","doi-asserted-by":"publisher","first-page":"e37467","DOI":"10.1371\/journal.pone.0037467","article-title":"Microtubule destabilization is shared by genetic and idiopathic Parkinson's disease patient fibroblasts","volume":"7","author":"Cartelli","year":"2012","journal-title":"PLoS One"},{"key":"2021111720333250200_B36","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/33416","article-title":"Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism","volume":"392","author":"Kitada","year":"1998","journal-title":"Nature"},{"key":"2021111720333250200_B37","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/77060","article-title":"Familial Parkinson's disease gene product parkin, is a ubiquitin-protein ligase","volume":"2","author":"Shimura","year":"2000","journal-title":"Nat. Genet."},{"key":"2021111720333250200_B38","doi-asserted-by":"publisher","first-page":"3053","DOI":"10.1007\/s00018-012-0978-5","article-title":"Regulation of Parkin E3 ligase activity","volume":"69","author":"Walden","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"2021111720333250200_B39","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.tins.2014.03.004","article-title":"Parkin and PINK1: much more than mitophagy","volume":"37","author":"Scarffe","year":"2014","journal-title":"Trends Neurosci."},{"key":"2021111720333250200_B40","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1074\/jbc.M112.391680","article-title":"PTEN-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem (iPS) cell-derived neurons","volume":"288","author":"Rakovic","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2021111720333250200_B41","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3389\/fneur.2013.00100","article-title":"Parkin- and PINK1-dependent mitophagy in neurons: will the real pathway please stand up?","volume":"4","author":"Grenier","year":"2013","journal-title":"Front. Neurol."},{"key":"2021111720333250200_B42","doi-asserted-by":"publisher","first-page":"5182","DOI":"10.1038\/ncomms6182","article-title":"Parkin regulates kainate receptors by interacting with the GluK2 subunit","volume":"5","author":"Maraschi","year":"2014","journal-title":"Nat. Commun."},{"key":"2021111720333250200_B43","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1523\/JNEUROSCI.23-08-03316.2003","article-title":"Parkin binds to \u03b1\/\u03b2 tubulin and increases their ubiquitination and degradation","volume":"23","author":"Ren","year":"2003","journal-title":"J. Neurosci."},{"key":"2021111720333250200_B44","doi-asserted-by":"publisher","first-page":"17154","DOI":"10.1074\/jbc.M500843200","article-title":"Parkin stabilizes microtubules through strong binding mediated by three independent domains","volume":"280","author":"Yang","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2021111720333250200_B45","doi-asserted-by":"publisher","first-page":"4009","DOI":"10.1074\/jbc.M806245200","article-title":"Parkin protects dopaminergic neurons against microtubule-depolymerizing toxins by attenuating microtubule-associated protein kinase activation","volume":"284","author":"Ren","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021111720333250200_B46","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.cell.2011.10.018","article-title":"PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility","volume":"147","author":"Wang","year":"2011","journal-title":"Cell"},{"key":"2021111720333250200_B47","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1002\/stem.1854","article-title":"Parkin mutations reduce the complexity of neuronal processes in iPSC derived human neurons","volume":"33","author":"Ren","year":"2015","journal-title":"Stem Cells"},{"key":"2021111720333250200_B48","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.2174\/138161211798072553","article-title":"Microtubules (tau) as an emerging therapeutic target: NAP (davunetide)","volume":"17","author":"Gozes","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"2021111720333250200_B49","doi-asserted-by":"publisher","first-page":"2937","DOI":"10.1093\/brain\/awt153","article-title":"Beyond taxol: microtubule-based treatment of disease and injury of the nervous system","volume":"136","author":"Baas","year":"2013","journal-title":"Brain"},{"key":"2021111720333250200_B50","doi-asserted-by":"publisher","first-page":"5040","DOI":"10.1016\/j.bmc.2013.12.046","article-title":"Microtubule-stabilizing agents as potential therapeutics for neurodegenerative disease","volume":"22","author":"Brunden","year":"2014","journal-title":"Bioorg. Med. Chem."}],"container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/43\/2\/292\/486182\/bst0430292.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/43\/2\/292\/486182\/bst0430292.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:42:30Z","timestamp":1637196150000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/43\/2\/292\/66401\/Linking-microtubules-to-Parkinson-s-disease-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,1]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,4,7]]},"published-print":{"date-parts":[[2015,4,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bst20150007","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,1]]}}}