ArticleHuman molecular genetics2016
Reduction of TMEM97 increases NPC1 protein levels and restores cholesterol trafficking in Niemann-pick type C1 disease cells.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- CT1812 biomarker signature from a meta-analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- TMEM97 regulates cholesterol biosynthesis and mitochondrial metabolism in gastric carcinoma.iScience · 2026Article
- Investigating the role of neuroglobin in cholesterol metabolism: a spotlight on brain-derived cells.Lipids in health and disease · 2026Article
- Dual sigma receptor 1 and 2 modulator improves memory behavior in mouse model of age-related cognitive decline.The Journal of pharmacology and experimental therapeutics · 2026Article
- Veraguamide E, a Marine Cyanobacterial Depsipeptide Targeting σJournal of natural products · 2025Article
- Transmembrane Protein 97 (TMEM97): Molecular Target and Treatment in Age-Related Macular Degeneration (AMD).Biomolecules · 2025Review
- Sigma‑2 Receptor/Transmembrane Protein 97 in Pain Modulation: Tracing Historical Roots and Current Research Directions.ACS pharmacology & translational science · 2025Review
- The Metabolic Signature of Autism Spectrum Disorders Using Dried Blood Spots at Birth.Psychiatry investigation · 2025Article
- TMEM97 governs partial epithelial-mesenchymal transition of retinal pigment epithelial cells via the CTNND2-ADAM10 axis.Molecular therapy. Nucleic acids · 2025Article
- Identifying the crucial binding domain of histatin-1 to recombinant TMEM97 in activating chemotactic migration in human corneal epithelial cells.Biochemical and biophysical research communications · 2024Article
- Roles for PMP22 in Schwann cell cholesterol homeostasis in health and disease.Biochemical Society transactions · 2024Review
- Article
- Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress.Cell death & disease · 2024Article
- High-content screening identifies a small molecule that restores AP-4-dependent protein trafficking in neuronal models of AP-4-associated hereditary spastic paraplegia.Nature communications · 2024Article
- Highly specific σProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Highly specific σbioRxiv : the preprint server for biology · 2023Article
- Sigma Receptors: Novel Regulators of Iron/Heme Homeostasis and Ferroptosis.International journal of molecular sciences · 2023Review
- Sigma-2 Receptors-From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases.International journal of molecular sciences · 2023Review
- Review
- Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons.Marine drugs · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Niemann-Pick type C disease (NP-C) is a progressive lysosomal lipid storage disease caused by mutations in the NPC1 and NPC2 genes. NPC1 is essential for transporting cholesterol and other lipids out of lysosomes, but little is known about the mechanisms that control its cellular abundance and localization. Here we show that a reduction of TMEM97, a cholesterol-responsive NPC1-binding protein, increases NPC1 levels in cells through a post-transcriptional mechanism. Reducing TMEM97 through RNA-interference reduces lysosomal lipid storage and restores cholesterol trafficking to the endoplasmic reticulum in cell models of NP-C. In TMEM97 knockdown cells, NPC1 levels can be reinstated with wild type TMEM97, but not TMEM97 missing an ER-retention signal suggesting that TMEM97 contributes to controlling the availability of NPC1 to the cell. Importantly, knockdown of TMEM97 also increases levels of residual NPC1 in NPC1-mutant patient fibroblasts and reduces cholesterol storage in an NPC1-dependent manner. Our findings propose TMEM97 inhibition as a novel strategy to increase residual NPC1 levels in cells and a potential therapeutic target for NP-C.
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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.