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.
Keywords: Autophagy; Huntington disease; Parkinson disease; TBC1D15; interferon-beta; miR-1; proteinopathies.