ArticleJournal of neuroinflammation2020
Mice defective in interferon signaling help distinguish between primary and secondary pathological pathways in a mouse model of neuronal forms of Gaucher disease.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Cumulative Antigen Suppression Reduces Clonal Plasma Cell Evolution in Gaucher Disease.American journal of hematology · 2026Article
- GBA1 F213I mutation increases the expression of LCN2 promoting neurodegeneration.Cell death and differentiation · 2026Article
- Deletion of Gba in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model.JCI insight · 2024Article
- Old disease-New reflections: Gaucher, immunity, and inflammation.Journal of cellular and molecular medicine · 2024Review
- Whole Transcriptome Analysis of Substantia Nigra in Mice with MPTP-Induced Parkinsonism Bearing Defective Glucocerebrosidase Activity.International journal of molecular sciences · 2023Article
- Article
- Consequences of excessive glucosylsphingosine in glucocerebrosidase-deficient zebrafish.Journal of lipid research · 2022Article
- Neuroinflammation in Gaucher disease, neuronal ceroid lipofuscinosis, and commonalities with Parkinson's disease.Brain research · 2022Review
- A multifaceted evaluation of microgliosis and differential cellular dysregulation of mammalian target of rapamycin signaling in neuronopathic Gaucher disease.Frontiers in molecular neuroscience · 2022Article
- C5a Activates a Pro-Inflammatory Gene Expression Profile in Human Gaucher iPSC-Derived Macrophages.International journal of molecular sciences · 2021Article
- Proteomics analysis of a human brain sample from a mucolipidosis type IV patient reveals pathophysiological pathways.Orphanet journal of rare diseases · 2021Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe type 1 interferon (IFN) response is part of the innate immune response and best known for its role in viral and bacterial infection. However, this pathway is also induced in sterile inflammation such as that which occurs in a number of neurodegenerative diseases, including neuronopathic Gaucher disease (nGD), a lysosomal storage disorder (LSD) caused by mutations in GBA.
methodsMice were injected with conduritol B-epoxide, an irreversible inhibitor of acid beta-glucosidase, the enzyme defective in nGD. MyTrMaSt null mice, where four adaptors of pathogen recognition receptors (PRRs) are deficient, were used to determine the role of the IFN pathway in nGD pathology. Activation of inflammatory and other pathways was analyzed by a variety of methods including RNAseq.
resultsElevation in the expression of PRRs associated with the IFN response was observed in CBE-injected mice. Ablation of upstream pathways leading to IFN production had no therapeutic benefit on the lifespan of nGD mice but attenuated neuroinflammation. Primary and secondary pathological pathways (i.e., those associated or not with mouse survival) were distinguished, and a set of ~210 genes including those related to sphingolipid, cholesterol, and lipoprotein metabolism, along with a number of inflammatory pathways related to chemokines, TNF, TGF, complement, IL6, and damage-associated microglia were classified as primary pathological pathways, along with some lysosomal and neuronal genes.
conclusionsAlthough IFN signaling is the top elevated pathway in nGD, we demonstrate that this pathway is not related to mouse viability and is consequently defined as a secondary pathology pathway. By elimination, we defined a number of critical pathways that are directly related to brain pathology in nGD, which in addition to its usefulness in understanding pathophysiological mechanisms, may also pave the way for the development of novel therapeutic paradigms by targeting such pathways.
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