IFNB/interferon-β regulates autophagy via a MIR1-TBC1D15-RAB7 pathway.
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Peer-reviewed
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Abstract
Loss of IFNB/interferon-β in mice causes a Parkinson disease-like phenotype where many features, including SNCA/α-synuclein and MAPT/tau accumulation, can be attributed to a late-stage block in autophagic flux. Recently, we identified a mechanism that can explain this phenotype. We found that IFNB induces expression of Mir1, a microRNA that can reduce the levels of TBC1D15, a RAB GTPase-activating protein. Induction of this pathway decreases RAB7 activity and thereby stimulates macroautophagy/autophagy. The relevance of these key players is deeply conserved from humans to Caenorhabditis elegans, highlighting the importance of this ancient autophagy regulatory pathway.
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Keywords
Autophagy, Huntington disease, Parkinson disease, TBC1D15, interferon-beta, miR-1, proteinopathies, Animals, Autophagy, GTPase-Activating Proteins, Humans, Interferon-beta, MicroRNAs, rab GTP-Binding Proteins
Journal Title
Autophagy
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Journal ISSN
1554-8627
1554-8635
1554-8635
Volume Title
16
Publisher
Informa UK Limited
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Sponsorship
Wellcome Trust (095317/Z/11/Z)
UK Dementia Research Institute at the University of Cambridge
(funded by the MRC, Alzheimer’s Research UK and the Alzheimer’s Society), the National
Institute for Health Research Cambridge Biomedical Research Centre, the Wellcome Trust
(095317/Z/11/Z), the Spoelberch Foundation and an anonymous donation to the Cambridge
Centre for Parkinson-Plus to D.C.R., NHMRC (Senior Research Fellowship GNT1137645
and Project Grant GNT1156481 to R.P.), veski Innovation Fellowship (VIF23 to R.P.), The
Danish Council for Independent Research (DFF - 6110-00461 to P.E.), Lundbeck
Foundation (R210-2015-3372 to P.E.), and Parkinsonforening in Denmark (to P.E.).