dc.contributor.author | Palacios, IM | |
dc.contributor.author | Palacios De Castro, MI | |
dc.contributor.editor | biorxiv team | |
dc.date.accessioned | 2024-05-10T08:33:24Z | |
dc.date.available | 2024-04-24 | |
dc.date.available | 2024-05-10T08:33:24Z | |
dc.date.issued | 2024-04-24 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/96768 | |
dc.description.abstract | Alzheimer’s Disease is the leading cause of dementia and the most common neurodegenerative disorder. Understanding the molecular pathology of Alzheimer’s Disease 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 β-amyloid (Aβ) carrying the E22G pathogenic “Arctic” mutation (Aβ42Arc) affects axonal health and behaviour of Drosophila. We find that Aβ42Arc flies present aberrant neurons, with altered axonal transport of mitochondrial and an increased number of terminal boutons at neuromuscular junctions. We demonstrate that the major axonal motor proteins kinesin-1 and kinesin-3 are essential for the correct development of neurons in Drosophila larvae and similar findings are replicated in human iPSC-derived cortical neurons. We then show that the over-expression of kinesin-1 or kinesin-3 restores the correct number of terminal boutons in Aβ42Arc expressing neurons and that this is associated with a rescue of the overall neuronal function, measured by negative geotaxis locomotor behavioural assay. We therefore provide new evidence in understanding the mechanisms of axonal transport defects in Alzheimer’s Disease, and our results indicate that kinesins should be considered as potential drug targets to help reduce dementia-associated disorders. | en_US |
dc.publisher | bioRxiv | en_US |
dc.relation.ispartof | bioRxiv journal | |
dc.subject | Alzheimer’s Disease, amyloid beta, neurodegeneration, axonal transport, motor proteins, Drosophila neurons, human neurons, iPSC. | en_US |
dc.title | Essential conserved neuronal motors kinesin-1 and kinesin-3 regulate Aβ42 toxicity in vivo | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1101/2024.04.23.590704 | |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
dcterms.dateAccepted | 2024-04-24 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
qmul.funder | A biophysical study on how the actin and microtubule cytoskeletons dynamically collaborate to regulate cellular organization::Biotechnology and Biological Sciences Research Council | en_US |
qmul.funder | A biophysical study on how the actin and microtubule cytoskeletons dynamically collaborate to regulate cellular organization::Biotechnology and Biological Sciences Research Council | en_US |
qmul.funder | A biophysical study on how the actin and microtubule cytoskeletons dynamically collaborate to regulate cellular organization::Biotechnology and Biological Sciences Research Council | en_US |
qmul.funder | A biophysical study on how the actin and microtubule cytoskeletons dynamically collaborate to regulate cellular organization::Biotechnology and Biological Sciences Research Council | en_US |