ArticleHuman molecular genetics2013
Sterol metabolism regulates neuroserpin polymer degradation in the absence of the unfolded protein response in the dementia FENIB.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Potential Role of Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) Abnormalities in Epileptogenesis: Multimodal Mechanisms and Therapeutic Targets.Molecular neurobiology · 2026Review
- Identification and Validation of Glycosylation‑Related Genes in Ischemic Stroke Based on Bioinformatics and Machine Learning.Journal of molecular neuroscience : MN · 2025Article
- Modeling and correction of protein conformational disease in iPSC-derived neurons through personalized base editing.Molecular therapy. Nucleic acids · 2025Article
- An Inducible Neural Stem Progenitor Cell Model for Testing Therapeutic Interventions Against Neurodegeneration FENIB.Drug development research · 2025Article
- UBE2J1 is identified as a novel plasma cell-related gene involved in the prognosis of high-grade serous ovarian cancer.Journal of translational medicine · 2025Article
- Expression of the Z Variant of α1-Antitrypsin Suppresses Hepatic Cholesterol Biosynthesis in Transgenic Zebrafish.International journal of molecular sciences · 2023Article
- Polymerogenic neuroserpin causes mitochondrial alterations and activates NFκB but not the UPR in a neuronal model of neurodegeneration FENIB.Cellular and molecular life sciences : CMLS · 2022Article
- Disruption of the Ubiquitin-Proteasome System and Elevated Endoplasmic Reticulum Stress in Epilepsy.Biomedicines · 2022Review
- Neuroserpin, a crucial regulator for axogenesis, synaptic modelling and cell-cell interactions in the pathophysiology of neurological disease.Cellular and molecular life sciences : CMLS · 2022Review
- Neuroserpin Inclusion Bodies in a FENIB Yeast Model.Microorganisms · 2021Article
- Neuroserpin polymers cause oxidative stress in a neuronal model of the dementia FENIB.Neurobiology of disease · 2017Article
- Cholesterol impairment contributes to neuroserpin aggregation.Scientific reports · 2017Article
- The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z-α1-antitrypsin.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Interactions between N-linked glycosylation and polymerisation of neuroserpin within the endoplasmic reticulum.The FEBS journal · 2015Article
- Functional and dysfunctional conformers of human neuroserpin characterized by optical spectroscopies and Molecular Dynamics.Biochimica et biophysica acta · 2015Article
- Icariin induces synoviolin expression through NFE2L1 to protect neurons from ER stress-induced apoptosis.PloS one · 2015Article
- Protein accumulation in the endoplasmic reticulum as a non-equilibrium phase transition.Nature communications · 2014Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Mutants of neuroserpin are retained as polymers within the endoplasmic reticulum (ER) of neurones to cause the autosomal dominant dementia familial encephalopathy with neuroserpin inclusion bodies or FENIB. The cellular consequences are unusual in that the ordered polymers activate the ER overload response (EOR) in the absence of the canonical unfolded protein response. We use both cell lines and Drosophila models to show that the G392E mutant of neuroserpin that forms polymers is degraded by UBE2j1 E2 ligase and Hrd1 E3 ligase while truncated neuroserpin, a protein that lacks 132 amino acids, is degraded by UBE2g2 (E2) and gp78 (E3) ligases. The degradation of G392E neuroserpin results from SREBP-dependent activation of the cholesterol biosynthetic pathway in cells that express polymers of neuroserpin (G392E). Inhibition of HMGCoA reductase, the limiting enzyme of the cholesterol biosynthetic pathway, reduced the ubiquitination of G392E neuroserpin in our cell lines and increased the retention of neuroserpin polymers in both HeLa cells and primary neurones. Our data reveal a reciprocal relationship between cholesterol biosynthesis and the clearance of mutant neuroserpin. This represents the first description of a link between sterol metabolism and modulation of the proteotoxicity mediated by the EOR.
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