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dc.contributor.authorBarker, Roger
dc.date.accessioned2021-12-16T00:30:49Z
dc.date.available2021-12-16T00:30:49Z
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331539
dc.description.abstractHuntington’s disease (HD) is a neurodegenerative disorder caused by CAG expansions in the huntingtin (HTT) gene. Modelling Huntington’s disease is challenging, as rodent and cellular models poorly recapitulate the disease as seen in aging humans. To address this, we generated induced neurons (iNs) through direct reprogramming of human skin fibroblasts, which retain age-dependent epigenetic characteristics. HD-iNs displayed profound deficits in autophagy, characterised by reduced transport of late autophagic structures from the neurites to the soma. These neurite-specific alterations in autophagy resulted in shorter, thinner and fewer neurites specifically in HD-iNs. CRISPRi-mediated silencing of HTT did not rescue this phenotype but rather resulted in additional autophagy alterations in ctrl-iNs, highlighting the importance of wild type HTT in normal neuronal autophagy. In summary, our work identifies a distinct subcellular autophagy impairment in adult patient derived Huntington’s disease neurons and provides a new rational for future development of autophagy activation therapies.
dc.publisherOxford University Press
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.subjectCambridge Stem Cell Institute
dc.titleDistinct sub-cellular autophagy impairments occur independently of protein aggregation in induced neurons from patients with Huntington’s disease
dc.typeArticle
dc.publisher.departmentDepartment of Clinical Neurosciences - Sci
dc.date.updated2021-12-14T17:40:06Z
prism.publicationNameBrain
dc.identifier.doi10.17863/CAM.78993
dcterms.dateAccepted2021-12-01
rioxxterms.versionAM
dc.contributor.orcidBarker, Roger [0000-0001-8843-7730]
dc.identifier.eissn1460-2156
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
cam.orpheus.counter15*
cam.depositDate2021-12-14
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2024-12-15


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