The study shows trehalose causes lysosomal membrane permeabilization (LMP) that paradoxically enhances autophagy rather than causing cytotoxicity. The molecular mechanisms preventing LMP-induced apoptosis while promoting beneficial autophagy remain unclear, which is critical for therapeutic safety. Gap type: unexplained_observation Source paper: Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration. (2019, Autophagy, PMID:30335591)
Landscape Summary: How does controlled lysosomal membrane permeabilization induce autophagy without triggering cell death? is a 0.85 priority gap in neurodegeneration. It has 0 linked hypotheses with average composite score 0.000. Status: partially_addressed.
Colonna, Sevlever, et al. (TREM2 biology)
How does controlled lysosomal membrane permeabilization induce autophagy without triggering cell death? — INVOKE-2 (completed)
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