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Article
| Open Access
Coordinate regulation of mutant NPC1 degradation by selective ER autophagy and MARCH6-dependent ERAD
Niemann-Pick type C1 disease is most commonly caused by the allele NPC1 I1061T, which is misfolded in the ER and rapidly degraded by the ubiquitin proteasome system. Here the authors show that the I1061T mutant is also degraded by ER-phagy.
- Mark L. Schultz
- , Kelsey L. Krus
- & Andrew P. Lieberman
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Article
| Open Access
Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures
Neurodegeneration is increasingly associated with endolysosomal and autophagy dysfunction. Here, Miranda and colleagues show that disruption of neuronal PI3P/Vps34 signaling leads to endolysosomal membrane damage and aberrant release of undigested material in APP-CTF- and BMP-positive exosomes.
- André M. Miranda
- , Zofia M. Lasiecka
- & Gilbert Di Paolo
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Article
| Open Access
Pathological roles of the VEGF/SphK pathway in Niemann–Pick type C neurons
Sphingosine is abnormally accumulated in Niemann–Pick type C disease (NP–C), but the causes of this accumulation have not been fully characterized. Here the authors show that sphingosine kinase activity is reduced in NP–C patient fibroblasts and NP–C mouse neurons due to defective vascular endothelial growth factor levels, suggesting therapeutic avenues.
- Hyun Lee
- , Jong Kil Lee
- & Hee Kyung Jin
Brainstem development requires galactosylceramidase and is critical for pathogenesis in a model of Krabbe disease