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  • Drouin-Ouellet, JanelleUniversity of Montreal (author)

Age-related pathological impairments in directly reprogrammed dopaminergic neurons derived from patients with idiopathic Parkinson's disease

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • Elsevier BV,2022

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:40fe8f96-0b25-4de5-8504-52bf18be55c4
  • https://lup.lub.lu.se/record/40fe8f96-0b25-4de5-8504-52bf18be55c4URI
  • https://doi.org/10.1016/j.stemcr.2022.08.010DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:151073587URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • We have developed an efficient approach to generate functional induced dopaminergic (DA) neurons from adult human dermal fibroblasts. When performing DA neuronal conversion of patient fibroblasts with idiopathic Parkinson's disease (PD), we could specifically detect disease-relevant pathology in these cells. We show that the patient-derived neurons maintain age-related properties of the donor and exhibit lower basal chaperone-mediated autophagy compared with healthy donors. Furthermore, stress-induced autophagy resulted in an age-dependent accumulation of macroautophagic structures. Finally, we show that these impairments in patient-derived DA neurons leads to an accumulation of phosphorylated alpha-synuclein, the classical hallmark of PD pathology. This pathological phenotype is absent in neurons generated from induced pluripotent stem cells from the same patients. Taken together, our results show that direct neural reprogramming can be used for obtaining patient-derived DA neurons, which uniquely function as a cellular model to study age-related pathology relevant to idiopathic PD.

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  • Legault, Emilie MUniversity of Montreal (author)
  • Nilsson, FredrikLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)fr5372ni (author)
  • Pircs, KarolinaLund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Molecular Neurogenetics,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)med-kpc (author)
  • Bouquety, JulieUniversity of Montreal (author)
  • Petit, FlorenceUniversity of Montreal (author)
  • Shrigley, ShelbyLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)sh3448sh (author)
  • Birtele, MarcellaLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)ma5203bi (author)
  • Pereira, MariaLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)med-mmp (author)
  • Storm, PetterLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)med-psm (author)
  • Sharma, YogitaLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)yo4230sh (author)
  • Bruzelius, AndreasLund University,Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Regenerativ neurofysiologi,Forskargrupper vid Lunds universitet,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine,Regenerative Neurophysiology,Lund University Research Groups(Swepub:lu)an1575br (author)
  • Vuono, RominaUniversity of Cambridge (author)
  • Kele, MalinKarolinska Institute (author)
  • Stoker, Thomas BUniversity of Cambridge (author)
  • Ottosson, Daniella RylanderLund University,Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Regenerativ neurofysiologi,Forskargrupper vid Lunds universitet,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine,Regenerative Neurophysiology,Lund University Research Groups(Swepub:lu)med-drr (author)
  • Falk, AnnaKarolinska Institutet,Karolinska Institute(Swepub:lu)an1083fa (author)
  • Jakobsson, JohanLund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Molecular Neurogenetics,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)mphy-jja (author)
  • Barker, Roger AUniversity of Cambridge(Swepub:lu)med-rob (author)
  • Parmar, MalinLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine(Swepub:lu)mphy-mpa (author)
  • University of MontrealUtvecklings- och regenerativ neurobiologi (creator_code:org_t)

Related titles

  • In:Stem Cell Reports: Elsevier BV17:10, s. 2203-22192213-6711

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