ArticleMolecular brain2013
Insufficient ER-stress response causes selective mouse cerebellar granule cell degeneration resembling that seen in congenital disorders of glycosylation.
Article in Molecular brain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Glycosylation disorders in pediatric epilepsy: pathophysiology, imaging and precision therapy.Frontiers in neurology · 2026Review
- O-GlcNAcylation modulates expression and abundance of N-glycosylation machinery in an inherited glycosylation disorder.Cell reports · 2024Article
- Deficient glycan extension and endoplasmic reticulum stresses in ALG3-CDG.Journal of inherited metabolic disease · 2024Article
- N-glycosylation as a eukaryotic protective mechanism against protein aggregation.Science advances · 2024Article
- Changes in tissue proteinPNAS nexus · 2024Article
- Liver transplantation recovers hepatic N-glycosylation with persistent IgG glycosylation abnormalities: Three-year follow-up in a patient with phosphomannomutase-2-congenital disorder of glycosylation.Molecular genetics and metabolism · 2023Article
- Effects of GRP78 on Endoplasmic Reticulum Stress and Inflammatory Response in Macrophages of Large Yellow Croaker (International journal of molecular sciences · 2023Article
- Endoplasmic Reticulum Stress Signaling and Neuronal Cell Death.International journal of molecular sciences · 2022Review
- A genome-wide CRISPR screen identifies DPM1 as a modifier of DPAGT1 deficiency and ER stress.PLoS genetics · 2022Article
- Oligomannose-Type Glycan Processing in the Endoplasmic Reticulum and Its Importance in Misfolding Diseases.Biology · 2022Review
- Precision genetic cellular models identify therapies protective against ER stress.Cell death & disease · 2021Article
- Diagnostic Approach to Cerebellar Hypoplasia.Cerebellum (London, England) · 2021Review
- Vascular ring anomaly in a patient with phosphomannomutase 2 deficiency: A case report and review of the literature.JIMD reports · 2020Article
- Caspase-3 Activation Correlates With the Initial Mitochondrial Membrane Depolarization in Neonatal Cerebellar Granule Neurons.Frontiers in cell and developmental biology · 2020Article
- Nrf2 activation attenuates genetic endoplasmic reticulum stress induced by a mutation in the phosphomannomutase 2 gene in zebrafish.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- DPAGT1-CDG: Functional analysis of disease-causing pathogenic mutations and role of endoplasmic reticulum stress.PloS one · 2017Article
- Endoplasmic Reticulum Stress and Ethanol Neurotoxicity.Biomolecules · 2015Review
- Neurological aspects of human glycosylation disorders.Annual review of neuroscience · 2015Review
- Endoplasmic reticulum chaperone GRP78 is involved in autophagy activation induced by ischemic preconditioning in neural cells.Molecular brain · 2015Article
- Neurodegeneration and unfolded-protein response in mice expressing a membrane-tethered flexible tail of PrP.PloS one · 2015Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCongenital disorders of glycosylation (CDGs) are inherited diseases caused by glycosylation defects. Incorrectly glycosylated proteins induce protein misfolding and endoplasmic reticulum (ER) stress. The most common form of CDG, PMM2-CDG, is caused by deficiency in the cytosolic enzyme phosphomannomutase 2 (PMM2). Patients with PMM2-CDG exhibit a significantly reduced number of cerebellar Purkinje cells and granule cells. The molecular mechanism underlying the specific cerebellar neurodegeneration in PMM2-CDG, however, remains elusive.
resultsHerein, we report that cerebellar granule cells (CGCs) are more sensitive to tunicamycin (TM)-induced inhibition of total N-glycan synthesis than cortical neurons (CNs). When glycan synthesis was inhibited to a comparable degree, CGCs exhibited more cell death than CNs. Furthermore, downregulation of PMM2 caused more CGCs to die than CNs. Importantly, we found that upon PMM2 downregulation or TM treatment, ER-stress response proteins were elevated less significantly in CGCs than in CNs, with the GRP78/BiP level showing the most significant difference. We further demonstrate that overexpression of GRP78/BiP rescues the death of CGCs resulting from either TM-treatment or PMM2 downregulation.
conclusionsOur results indicate that the selective susceptibility of cerebellar neurons to N-glycosylation defects is due to these neurons' inefficient response to ER stress, providing important insight into the mechanisms of selective neurodegeneration observed in CDG patients.
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