{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T01:56:28Z","timestamp":1781315788602,"version":"3.54.1"},"reference-count":86,"publisher":"The Royal Society","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004815","name":"Isaac Newton Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004815","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC"},{"name":"VLH"},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Paris Region fellowship"},{"name":"European Commission FP7"},{"DOI":"10.13039\/100009148","name":"Queen Mary University of London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009148","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Paris Region"},{"DOI":"10.13039\/501100000319","name":"Alzheimer's Research Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease (AD) is the leading cause of dementia and the most common neurodegenerative disorder. Understanding the molecular pathology of AD may help identify new ways to reduce neuronal damage. In the past decades, Drosophila has become a powerful tool in modelling mechanisms underlying human diseases. Here, we investigate how the expression of the human 42-residue \u03b2-amyloid (A\u03b2) carrying the E22G pathogenic \u2018Arctic\u2019 mutation (A\u03b242Arc) affects axonal health and behaviour in Drosophila. We find that A\u03b242Arc flies present aberrant neurons, with altered axonal transport of mitochondria and aberrant terminal boutons at neuromuscular junctions. We demonstrate that the motor proteins kinesin-1 and kinesin-3 are essential for the correct development of neurons in Drosophila larvae and in human induced pluripotent stem cell-derived cortical neurons. We then show that the overexpression of kinesin-1 or kinesin-3 restores the correct number and morphology of boutons in A\u03b242Arc-expressing neurons and rescues neuronal function measured by negative geotaxis locomotor behavioural assay. We therefore provide new evidence towards understanding the mechanisms of axonal transport defects in AD, and our results support the idea that kinesins should be considered as potential drug targets to help reduce dementia-associated disorders.<\/jats:p>","DOI":"10.1098\/rsob.250319","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:13:32Z","timestamp":1778631212000},"source":"Crossref","is-referenced-by-count":1,"title":["Investigating how changes in the levels of kinesins impact neuronal health in\n                    <i>Drosophila<\/i>\n                    and human iPSC-derived neurons AD model"],"prefix":"10.1098","volume":"16","author":[{"given":"Deepthy","family":"Francis","sequence":"first","affiliation":[{"name":"University of Cambridge 1 , ,","place":["Cambridge, UK"]},{"name":"Gilead Sciences Inc. 2 , , ,","place":["Foster City, CA, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Paonessa","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 , ,","place":["Cambridge, UK"]},{"name":"Talisman Therapeutics Ltd 3 , ,","place":["Cambridge, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2997-6499","authenticated-orcid":false,"given":"Victoria L.","family":"Hewitt","sequence":"additional","affiliation":[{"name":"University of Auckland - City Campus 4 , ,","place":["Auckland, New Zealand"]},{"name":"MRC Mitochondrial Biology Unit 5 , ,","place":["Cambridge, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Southall","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 , ,","place":["Cambridge, UK"]},{"name":"Royal Society of Chemistry 6 , ,","place":["London, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Peset","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 , ,","place":["Cambridge, UK"]},{"name":"CNIO 7 , ,","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Whitworth","sequence":"additional","affiliation":[{"name":"MRC Mitochondrial Biology Unit 5 , ,","place":["Cambridge, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick J.","family":"Livesey","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 , ,","place":["Cambridge, UK"]},{"name":"Talisman Therapeutics Ltd 3 , ,","place":["Cambridge, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6159-8689","authenticated-orcid":false,"given":"Caroline C. G.","family":"Fabre","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 , ,","place":["Cambridge, UK"]},{"name":"INRAE, Sorbonne Universit\u00e9, CNRS, IRD, UPEC, Universit\u00e9 Paris Cit\u00e9, iEES-Paris 8 , ,","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3450-7884","authenticated-orcid":false,"given":"Isabel M.","family":"Palacios","sequence":"additional","affiliation":[{"name":"Queen Mary University of London 9 , ,","place":["London, UK"],"department":["School of Biological and Behavioural Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"2026051416133859100_R1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"2026051416133859100_R2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer\u2019s disease","volume":"25","author":"Lane","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"2026051416133859100_R3","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1038\/emboj.2013.207","article-title":"Amyloid-\u03b2 oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin","volume":"32","author":"Zempel","year":"2013","journal-title":"EMBO J."},{"key":"2026051416133859100_R4","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13024-015-0064-1","article-title":"Tau missorting and spastin-induced microtubule disruption in neurodegeneration: Alzheimer disease and hereditary spastic paraplegia","volume":"10","author":"Zempel","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"2026051416133859100_R5","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.nbd.2017.04.010","article-title":"Regulation of motor proteins, axonal transport deficits and adult-onset neurodegenerative diseases","volume":"105","author":"Brady","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"2026051416133859100_R6","doi-asserted-by":"crossref","first-page":"8967","DOI":"10.1523\/JNEUROSCI.23-26-08967.2003","article-title":"Glutamate and amyloid beta-protein rapidly inhibit fast axonal transport in cultured rat hippocampal neurons by different mechanisms","volume":"23","author":"Hiruma","year":"2003","journal-title":"J. Neurosci."},{"key":"2026051416133859100_R7","doi-asserted-by":"crossref","first-page":"9166","DOI":"10.1523\/JNEUROSCI.1074-10.2010","article-title":"Amyloid-beta peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3beta in primary cultured hippocampal neurons","volume":"30","author":"Decker","year":"2010","journal-title":"J. Neurosci."},{"key":"2026051416133859100_R8","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/j.1600-0854.2012.01340.x","article-title":"Early and selective impairments in axonal transport kinetics of synaptic cargoes induced by soluble amyloid \u03b2-protein oligomers","volume":"13","author":"Tang","year":"2012","journal-title":"Traffic"},{"key":"2026051416133859100_R9","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/ahg.12554","article-title":"Using Drosophila amyloid toxicity models to study Alzheimer\u2019s disease","volume":"88","author":"Tsintzas","year":"2024","journal-title":"Ann. Hum. Genet."},{"key":"2026051416133859100_R10","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.neuroscience.2004.12.025","article-title":"Intraneuronal Abeta, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimer\u2019s disease","volume":"132","author":"Crowther","year":"2005","journal-title":"Neuroscience"},{"key":"2026051416133859100_R11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.mcn.2004.03.001","article-title":"A model for studying Alzheimer\u2019s Abeta42-induced toxicity in Drosophila melanogaster","volume":"26","author":"Finelli","year":"2004","journal-title":"Mol. Cell. Neurosci."},{"key":"2026051416133859100_R12","doi-asserted-by":"crossref","first-page":"6623","DOI":"10.1073\/pnas.0400895101","article-title":"Dissecting the pathological effects of human Abeta40 and Abeta42 in Drosophila: a potential model for Alzheimer\u2019s disease","volume":"101","author":"Iijima","year":"2004","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2026051416133859100_R13","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.coph.2004.07.001","article-title":"Therapeutic targets from a Drosophila model of Alzheimer\u2019s disease","volume":"4","author":"Crowther","year":"2004","journal-title":"Curr. Opin. Pharmacol."},{"key":"2026051416133859100_R14","doi-asserted-by":"crossref","first-page":"3899","DOI":"10.1523\/JNEUROSCI.0283-04.2004","article-title":"Age-dependent neurodegeneration and Alzheimer-amyloid plaque formation in transgenic Drosophila","volume":"24","author":"Greeve","year":"2004","journal-title":"J. Neurosci."},{"key":"2026051416133859100_R15","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1523\/JNEUROSCI.3699-09.2010","article-title":"Expression of beta-amyloid induced age-dependent presynaptic and axonal changes in Drosophila","volume":"30","author":"Zhao","year":"2010","journal-title":"J. Neurosci"},{"key":"2026051416133859100_R16","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nn0901-887","article-title":"The \u2018Arctic\u2019 APP mutation (E693G) causes Alzheimer\u2019s disease by enhanced Abeta protofibril formation","volume":"4","author":"Nilsberth","year":"2001","journal-title":"Nat. Neurosci."},{"key":"2026051416133859100_R17","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1001087","article-title":"Inhibition of GSK-3 ameliorates Abeta pathology in an adult-onset Drosophila model of Alzheimer\u2019s disease","volume":"6","author":"Sofola","year":"2010","journal-title":"PLoS Genet."},{"key":"2026051416133859100_R18","doi-asserted-by":"crossref","first-page":"5907","DOI":"10.1073\/pnas.0901229106","article-title":"Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta","volume":"106","author":"Pigino","year":"2009","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2026051416133859100_R19","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1091\/mbc.11.4.1213","article-title":"Axonal membrane proteins are transported in distinct carriers: a two-color video microscopy study in cultured hippocampal neurons","volume":"11","author":"Kaether","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"2026051416133859100_R20","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.semcdb.2019.07.010","article-title":"Axonal transport defects and neurodegeneration: molecular mechanisms and therapeutic implications","volume":"99","author":"Guo","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"2026051416133859100_R21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/cm.21657","article-title":"A common theme for axonopathies? The dependency cycle of local axon homeostasis","volume":"78","author":"Prokop","year":"2021","journal-title":"Cytoskeleton"},{"key":"2026051416133859100_R22","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.nbd.2019.03.021","article-title":"Amyloid beta-mediated KIF5A deficiency disrupts anterograde axonal mitochondrial movement","volume":"127","author":"Wang","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"2026051416133859100_R23","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0896-6273(00)00124-0","article-title":"Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I","volume":"28","author":"Kamal","year":"2000","journal-title":"Neuron"},{"key":"2026051416133859100_R24","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1093\/hmg\/dds109","article-title":"Calsyntenin-1 mediates axonal transport of the amyloid precursor protein and regulates A\u03b2 production","volume":"21","author":"Vagnoni","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2026051416133859100_R25","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1083\/jcb.201302078","article-title":"JIP1 regulates the directionality of APP axonal transport by coordinating kinesin and dynein motors","volume":"202","author":"Fu","year":"2013","journal-title":"J. Cell Biol."},{"key":"2026051416133859100_R26","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nrn2839","article-title":"100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future","volume":"11","author":"Bellen","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"2026051416133859100_R27","doi-asserted-by":"crossref","first-page":"R192","DOI":"10.1016\/j.cub.2008.01.015","article-title":"The origins of behavioral genetics","volume":"18","author":"Greenspan","year":"2008","journal-title":"Curr. Biol."},{"key":"2026051416133859100_R28","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1126\/science.287.5461.2204","article-title":"Comparative genomics of the eukaryotes","volume":"287","author":"Rubin","year":"2000","journal-title":"Science"},{"key":"2026051416133859100_R29","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/nn1936","article-title":"A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport","volume":"10","author":"Pack-Chung","year":"2007","journal-title":"Nat. Neurosci."},{"key":"2026051416133859100_R30","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1126\/science.289.5487.2120","article-title":"A function for kinesin I in the posterior transport of oskar mRNA and Staufen protein","volume":"289","author":"Brendza","year":"2000","journal-title":"Science"},{"key":"2026051416133859100_R31","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0896-6273(00)80701-1","article-title":"Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis","volume":"22","author":"Lee","year":"1999","journal-title":"Neuron"},{"key":"2026051416133859100_R32","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1038\/nprot.2012.116","article-title":"Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks","volume":"7","author":"Shi","year":"2012","journal-title":"Nat. Protoc."},{"key":"2026051416133859100_R33","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nn.3041","article-title":"Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses","volume":"15","author":"Shi","year":"2012","journal-title":"Nat. Neurosci."},{"key":"2026051416133859100_R34","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0143-22.2022","article-title":"Spontaneous cell cluster formation in human iPSC-derived neuronal spheroid networks influences network activity","volume":"9","author":"H\u00f6rberg","year":"2022","journal-title":"eNeuro"},{"key":"2026051416133859100_R35","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00726-007-0618-9","article-title":"Protein expression of BACE1, BACE2 and APP in Down syndrome brains","volume":"35","author":"Cheon","year":"2008","journal-title":"Amino Acids"},{"key":"2026051416133859100_R36","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1212\/WNL.35.7.957","article-title":"Alzheimer\u2019s disease in Down\u2019s syndrome: clinicopathologic studies","volume":"35","author":"Wisniewski","year":"1985","journal-title":"Neurology"},{"key":"2026051416133859100_R37","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neurobiolaging.2017.04.006","article-title":"Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline","volume":"56","author":"Cole","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"2026051416133859100_R38","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/00019052-200404000-00003","article-title":"Down syndrome and beta-amyloid deposition","volume":"17","author":"Head","year":"2004","journal-title":"Curr. Opin. Neurol."},{"key":"2026051416133859100_R39","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.celrep.2018.04.040","article-title":"Extracellular forms of A\u03b2 and Tau from iPSC models of Alzheimer\u2019s disease disrupt synaptic plasticity","volume":"23","author":"Hu","year":"2018","journal-title":"Cell Rep."},{"key":"2026051416133859100_R40","first-page":"1","article-title":"Plasma Abeta42\/40 ratio detects early stages of Alzheimer\u2019s disease and correlates with csf and neuroimaging biomarkers in the AB255 study","volume":"6","author":"P\u00e9rez-Grijalba","year":"2019","journal-title":"J. Prev. Alzheimer\u2019s Dis"},{"key":"2026051416133859100_R41","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/35086072","article-title":"Alzheimer\u2019s disease and Abeta toxicity: from top to bottom","volume":"2","author":"Small","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"2026051416133859100_R42","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1073\/pnas.0608332104","article-title":"The presenilin hypothesis of Alzheimer\u2019s disease: evidence for a loss-of-function pathogenic mechanism","volume":"104","author":"Shen","year":"2007","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2026051416133859100_R43","first-page":"373","article-title":"Synaptic abnormalities in a Drosophila model of Alzheimer\u2019s disease","volume":"7","author":"Mhatre","year":"2014","journal-title":"Dis. Model. Mech."},{"key":"2026051416133859100_R44","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1096\/fj.08-121152","article-title":"Distinctive roles of different beta-amyloid 42 aggregates in modulation of synaptic functions","volume":"23","author":"Chiang","year":"2009","journal-title":"FASEB J."},{"key":"2026051416133859100_R45","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/0896-6273(95)90141-8","article-title":"Wiring by fly: the neuromuscular system of the Drosophila embryo","volume":"15","author":"Bate","year":"1995","journal-title":"Neuron"},{"key":"2026051416133859100_R46","doi-asserted-by":"crossref","first-page":"3465","DOI":"10.1152\/jn.1997.78.6.3465","article-title":"Imaging of calcium in Drosophila larval motor nerve terminals","volume":"78","author":"Karunanithi","year":"1997","journal-title":"J. Neurophysiol."},{"key":"2026051416133859100_R47","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.neuron.2004.06.029","article-title":"Dap160\/intersectin acts as a stabilizing scaffold required for synaptic development and vesicle endocytosis","volume":"43","author":"Koh","year":"2004","journal-title":"Neuron"},{"key":"2026051416133859100_R48","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0008310","article-title":"Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer\u2019s disease","volume":"4","author":"Iijima-Ando","year":"2009","journal-title":"PLoS One"},{"key":"2026051416133859100_R49","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1091\/mbc.e05-06-0526","article-title":"Kinesin-1 and Dynein are the primary motors for fast transport of mitochondria in Drosophila motor axons","volume":"17","author":"Pilling","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"2026051416133859100_R50","doi-asserted-by":"crossref","DOI":"10.3791\/50339-v","article-title":"Assessing neurodegenerative phenotypes in Drosophila dopaminergic neurons by climbing assays and whole brain immunostaining","author":"Barone","year":"2013","journal-title":"J. Vis. Exp."},{"key":"2026051416133859100_R51","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1086\/344210","article-title":"A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10)","volume":"71","author":"Reid","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"2026051416133859100_R52","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1003066","article-title":"Spastic paraplegia mutation N256S in the neuronal microtubule motor KIF5A disrupts axonal transport in a Drosophila HSP model","volume":"8","author":"F\u00fcger","year":"2012","journal-title":"PLoS Genet."},{"key":"2026051416133859100_R53","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1002\/ana.24744","article-title":"KIF5A mutations cause an infantile onset phenotype including severe myoclonus with evidence of mitochondrial dysfunction","volume":"80","author":"Duis","year":"2016","journal-title":"Ann. Neurol."},{"key":"2026051416133859100_R54","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s13258-017-0612-x","article-title":"Wide phenotypic spectrum in axonal Charcot\u2013Marie\u2013Tooth neuropathy type 2 patients with KIF5A mutations","volume":"40","author":"Nam","year":"2018","journal-title":"Genes Genom."},{"key":"2026051416133859100_R55","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1016\/j.neuron.2018.02.027","article-title":"Genome-wide analyses identify KIF5A as a novel ALS gene","volume":"97","author":"Nicolas","year":"2018","journal-title":"Neuron"},{"key":"2026051416133859100_R56","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/jhg.2014.80","article-title":"KIF1A mutation in a patient with progressive neurodegeneration","volume":"59","author":"Okamoto","year":"2014","journal-title":"J. Hum. Genet."},{"key":"2026051416133859100_R57","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1136\/jmedgenet-2020-107007","article-title":"Heterozygous KIF1A variants underlie a wide spectrum of neurodevelopmental and neurodegenerative disorders","volume":"58","author":"Nicita","year":"2021","journal-title":"J. Med. Genet."},{"key":"2026051416133859100_R58","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1083\/jcb.141.2.431","article-title":"Defect in synaptic vesicle precursor transport and neuronal cell death in KIF1A motor protein-deficient mice","volume":"141","author":"Yonekawa","year":"1998","journal-title":"J. Cell Biol."},{"key":"2026051416133859100_R59","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.neuron.2016.05.002","article-title":"The molecular motor KIF1A transports the trka neurotrophin receptor and is essential for sensory neuron survival and function","volume":"90","author":"Tanaka","year":"2016","journal-title":"Neuron"},{"key":"2026051416133859100_R60","doi-asserted-by":"crossref","first-page":"14717","DOI":"10.1523\/JNEUROSCI.2770-14.2014","article-title":"Unique function of Kinesin Kif5A in localization of mitochondria in axons","volume":"34","author":"Campbell","year":"2014","journal-title":"J. Neurosci."},{"key":"2026051416133859100_R61","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1083\/jcb.200301026","article-title":"Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A","volume":"161","author":"Xia","year":"2003","journal-title":"J. Cell Biol."},{"key":"2026051416133859100_R62","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.neuron.2012.10.012","article-title":"Molecular motor KIF5A is essential for GABA(A) receptor transport, and KIF5A deletion causes epilepsy","volume":"76","author":"Nakajima","year":"2012","journal-title":"Neuron"},{"key":"2026051416133859100_R63","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1091\/mbc.e07-03-0261","article-title":"Identification of an axonal kinesin-3 motor for fast anterograde vesicle transport that facilitates retrograde transport of neuropeptides","volume":"19","author":"Barkus","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"2026051416133859100_R64","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1152\/physrev.00023.2007","article-title":"Intracellular transport and kinesin superfamily proteins, KIFs: structure, function, and dynamics","volume":"88","author":"Hirokawa","year":"2008","journal-title":"Physiol. Rev."},{"key":"2026051416133859100_R65","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1093\/genetics\/144.3.1075","article-title":"Kinesin mutations cause motor neuron disease phenotypes by disrupting fast axonal transport in Drosophila","volume":"144","author":"Hurd","year":"1996","journal-title":"Genetics"},{"key":"2026051416133859100_R66","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.61302","article-title":"Concerted action of kinesins KIF5B and KIF13B promotes efficient secretory vesicle transport to microtubule plus ends","volume":"9","author":"Serra-Marques","year":"2020","journal-title":"eLife"},{"key":"2026051416133859100_R67","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1177\/1073858412451655","article-title":"Role of kinesin-1 in the pathogenesis of SPG10, a rare form of hereditary spastic paraplegia","volume":"19","author":"Kawaguchi","year":"2013","journal-title":"Neuroscientist"},{"key":"2026051416133859100_R68","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/ng.2613","article-title":"Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly","volume":"45","author":"Poirier","year":"2013","journal-title":"Nat. Genet."},{"key":"2026051416133859100_R69","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0896-6273(01)00496-2","article-title":"Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila","volume":"32","author":"Gunawardena","year":"2001","journal-title":"Neuron"},{"key":"2026051416133859100_R70","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1073\/pnas.1307345111","article-title":"Transcriptome analysis of distinct mouse strains reveals kinesin light chain-1 splicing as an amyloid-\u03b2 accumulation modifier","volume":"111","author":"Morihara","year":"2014","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2026051416133859100_R71","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3233\/JAD-170094","article-title":"Overexpression of kinesin superfamily motor proteins in Alzheimer\u2019s disease","volume":"60","author":"Hares","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"2026051416133859100_R72","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2022.105288","article-title":"Increased KIF11\/kinesin-5 expression offsets Alzheimer A\u03b2-mediated toxicity and cognitive dysfunction","volume":"25","author":"Lucero","year":"2022","journal-title":"iScience"},{"key":"2026051416133859100_R73","doi-asserted-by":"crossref","first-page":"19540","DOI":"10.1038\/s41598-024-70543-y","article-title":"The ALS-associated KIF5A P986L variant is not pathogenic for Drosophila motoneurons","volume":"14","author":"Layalle","year":"2024","journal-title":"Sci. Rep."},{"key":"2026051416133859100_R74","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a006189","article-title":"Neuropathological alterations in Alzheimer disease","volume":"1","author":"Serrano-Pozo","year":"2011","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"2026051416133859100_R75","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1365-2990.2012.01308.x","article-title":"Review: axon pathology in age-related neurodegenerative disorders","volume":"39","author":"Adalbert","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"2026051416133859100_R76","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1093\/brain\/aws133","article-title":"Alterations in axonal transport motor proteins in sporadic and experimental Parkinson\u2019s disease","volume":"135","author":"Chu","year":"2012","journal-title":"Brain"},{"key":"2026051416133859100_R77","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1242\/dev.00503","article-title":"Targeted ablation of CCAP neuropeptide-containing neurons of Drosophila causes specific defects in execution and circadian timing of ecdysis behavior","volume":"130","author":"Park","year":"2003","journal-title":"Development"},{"key":"2026051416133859100_R78","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1534\/genetics.106.063461","article-title":"A new family of Drosophila balancer chromosomes with a w- dfd-GMR yellow fluorescent protein marker","volume":"174","author":"Le","year":"2006","journal-title":"Genetics"},{"key":"2026051416133859100_R79","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"2026051416133859100_R80","doi-asserted-by":"crossref","first-page":"5245","DOI":"10.1038\/ncomms6245","article-title":"Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations","volume":"5","author":"Godena","year":"2014","journal-title":"Nat. Commun."},{"key":"2026051416133859100_R81","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0076-6879(09)05018-6","article-title":"Imaging axonal transport of mitochondria","volume":"457","author":"Wang","year":"2009","journal-title":"Methods Enzymol."},{"key":"2026051416133859100_R82","doi-asserted-by":"crossref","DOI":"10.26508\/lsa.202201531","article-title":"Decreasing pdzd8-mediated mito-ER contacts improves organismal fitness and mitigates A\u03b242 toxicity","volume":"5","author":"Hewitt","year":"2022","journal-title":"Life Sci. Alliance"},{"key":"2026051416133859100_R83","doi-asserted-by":"crossref","DOI":"10.14440\/jbm.2014.36","article-title":"Advanced methods of microscope control using \u03bcManager software","volume":"1","author":"Edelstein","year":"2014","journal-title":"J. Biol. Methods"},{"key":"2026051416133859100_R84","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cub.2013.01.072","article-title":"bantam miRNA promotes systemic growth by connecting insulin signaling and ecdysone production","volume":"23","author":"Boulan","year":"2013","journal-title":"Curr. Biol."},{"key":"2026051416133859100_R85","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1006\/dbio.1993.1315","article-title":"Molecular analysis of the initiation of insect metamorphosis: a comparative study of Drosophila ecdysteroid-regulated transcription","volume":"160","author":"Andres","year":"1993","journal-title":"Dev. Biol."},{"key":"2026051416133859100_R86","doi-asserted-by":"crossref","DOI":"10.1038\/srep15298","article-title":"Impaired climbing and flight behaviour in Drosophila melanogaster following carbon dioxide anaesthesia","volume":"5","author":"Bartholomew","year":"2015","journal-title":"Sci. Rep."}],"container-title":["Open Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/rsob\/article-pdf\/doi\/10.1098\/rsob.250319\/6137580\/rsob.250319.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/royalsocietypublishing.org\/rsob\/article-pdf\/doi\/10.1098\/rsob.250319\/6137580\/rsob.250319.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T20:14:00Z","timestamp":1778789640000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/rsob\/article\/16\/5\/250319\/481673\/Investigating-how-changes-in-the-levels-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":86,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,13]]}},"URL":"https:\/\/doi.org\/10.1098\/rsob.250319","relation":{"has-review":[{"id-type":"doi","id":"10.1098\/RSOB.250319\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.250319\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.250319\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.250319\/v1\/decision1","asserted-by":"object"}]},"ISSN":["2046-2441"],"issn-type":[{"value":"2046-2441","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]},"article-number":"250319"}}