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Impact of different...
Impact of differential and time-dependent autophagy activation on therapeutic efficacy in a model of Huntington disease
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- Brattås, Per Ludvik (författare)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Wallenberg Neurocentrum, Lund,Molecular Neurogenetics,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Wallenberg Neuroscience Centre, Lund
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- Hersbach, Bob A. (författare)
- Lund University
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- Madsen, Sofia (författare)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Wallenberg Neurocentrum, Lund,Molecular Neurogenetics,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Wallenberg Neuroscience Centre, Lund
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- Petri, Rebecca (författare)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Wallenberg Neurocentrum, Lund,Molecular Neurogenetics,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Wallenberg Neuroscience Centre, Lund
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- Jakobsson, Johan (författare)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Wallenberg Neurocentrum, Lund,Molecular Neurogenetics,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Wallenberg Neuroscience Centre, Lund
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- Pircs, Karolina (författare)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Wallenberg Neurocentrum, Lund,Molecular Neurogenetics,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Wallenberg Neuroscience Centre, Lund
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(creator_code:org_t)
- 2020-05-06
- 2021
- Engelska 14 s.
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8627 .- 1554-8635. ; 17:6, s. 1316-1329
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http://dx.doi.org/10... (free)
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https://www.tandfonl...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Activation of macroautophagy/autophagy, a key mechanism involved in the degradation and removal of aggregated proteins, can successfully reverse Huntington disease phenotypes in various model systems. How neuronal autophagy impairments need to be considered in Huntington disease progression to achieve a therapeutic effect is currently not known. In this study, we used a mouse model of HTT (huntingtin) protein aggregation to investigate how different methods and timing of autophagy activation influence the efficacy of autophagy-activating treatment in vivo. We found that overexpression of human TFEB, a master regulator of autophagy, did not decrease mutant HTT aggregation. On the other hand, Becn1 overexpression, an autophagic regulator that plays a key role in autophagosome formation, partially cleared mutant HTT aggregates and restored neuronal pathology, but only when administered early in the disease progression. When Becn1 was administered at a later stage, when prominent mutant HTT accumulation and autophagy impairments have occurred, Becn1 overexpression did not rescue the mutant HTT-associated phenotypes. Together, these results demonstrate that the targets used to activate autophagy, as well as the timing of autophagy activation, are crucial for achieving efficient therapeutic effects.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Adeno-associated viral vectors
- autophagy
- BECN1/beclin-1
- Huntington disease
- macroautophagy
- neurodegeneration
- TFEB
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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