ArticleCell death and differentiation2014
High sphingomyelin levels induce lysosomal damage and autophagy dysfunction in Niemann Pick disease type A.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 3 of them syntheses that pooled it.
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Who cites it
98 citing papers in PubMed, 3 syntheses or guidelines pooled it, 170 citations in OpenAlex.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Systematic Analysis of Plasma-Derived Extracellular Vesicle-Enriched Samples in Age-Related Macular Degeneration Reveals Oxidative Stress Linked to Altered Lipid and Protein Profiles.Journal of extracellular biology · 2026Article
- The Sphingolipid Balance and Endothelial Dysfunction in Lysosomal Storage Diseases: Shared Mechanisms in Gaucher, Niemann-Pick and Fabry Disease.International journal of molecular sciences · 2026Review
- Contradictory Effects on Hepatocytes in ASMD.International journal of molecular sciences · 2026Review
- Pathogenic variants in BORCS5 cause a spectrum of neurodevelopmental and neurodegenerative disorders with lysosomal dysfunction.The Journal of clinical investigation · 2026Article
- Endolysosomal Impact of Elevated Ceramide Levels Revealed by Optical and Ultrastructural Nanoprobing.ACS nano · 2026Article
- Restoration of lysosomal membrane integrity in cell models of Pompe disease depends on fatty acid synthase and its product palmitic acid.Cellular & molecular biology letters · 2026Article
- WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson's Disease.bioRxiv : the preprint server for biology · 2026Article
- Obinutuzumab induces lysosomal destabilization via sphingomyelin-dependent inhibition of TRPML2.Scientific reports · 2026Article
- AXL Promotes Ischemic Myelin Repair Through Alleviating Myelin Debris Deposition and Lipid Droplets Accumulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lysosomal membrane homeostasis and its importance in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Review
- Hepatic ceramide synthesis links systemic inflammation to organelle dysfunction in cancer.bioRxiv : the preprint server for biology · 2025Article
- Acid sphingomyelinase is a gatekeeper of placental labyrinthine architecture and function.Development (Cambridge, England) · 2025Article
- Bidirectional causal associations between plasma metabolites and bipolar disorder.Molecular psychiatry · 2025Article
- Lysosomal quality control Review.Autophagy · 2025Review
- Linear ubiquitination at damaged lysosomes induces local NFKB activation and controls cell survival.Autophagy · 2025Article
- Lysosomal Repair in Health and Disease.Journal of cellular physiology · 2025Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Niemann Pick disease type A (NPA), which is caused by loss of function mutations in the acid sphingomyelinase (ASM) gene, is a lysosomal storage disorder leading to neurodegeneration. Yet, lysosomal dysfunction and its consequences in the disease are poorly characterized. Here we show that undegraded molecules build up in neurons of acid sphingomyelinase knockout mice and in fibroblasts from NPA patients in which autophagolysosomes accumulate. The latter is not due to alterations in autophagy initiation or autophagosome-lysosome fusion but because of inefficient autophago-lysosomal clearance. This, in turn, can be explained by lysosomal membrane permeabilization leading to cytosolic release of Cathepsin B. High sphingomyelin (SM) levels account for these effects as they can be induced in control cells on addition of the lipid and reverted on SM-lowering strategies in ASM-deficient cells. These results unveil a relevant role for SM in autophagy modulation and characterize autophagy anomalies in NPA, opening new perspectives for therapeutic interventions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.