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Article

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Accepted version

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2016-02-01

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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/148464

Limited unfolded protein response and inflammation in neuroserpinopathy

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https://doi.org/10.1093/jnen/nlv011

Abstract

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare disease characterized by the deposition of multiple intracytoplasmic neuronal inclusions that contain mutated neuroserpin. Tg-Syracuse (Tg-Syr) mice express Ser49Pro mutated neuroserpin and develop clinical and neuropathological features of human FENIB. We used 8-, 34-, 45- and 80-week-old Tg-Syr mice to characterize neuroinflammation and the unfolded protein response (UPR) in a neurodegenerative disease in which abnormal protein aggregates accumulate within the endoplasmic reticulum (ER). There were scattered neuroserpin inclusions in Tg-Syr mice at 8 weeks of age; the numbers of neurons involved and the amount of neuroserpin per neuron increased with age throughout the CNS to 80 weeks of age; no similar inclusions were found in wild type (Tg-WT) mice at any age. Increases in numbers of astrocytes and microglia occurred at advanced disease stages. Among 22 markers in 80-week-old Tg-Syr mice, only II1b and II10rb mRNAs in the somatosensory cortex and CxCl10 and Il10rb mRNAs in the olfactory bulb were upregulated when compared with Tg-WT mice indicating a limited relationship between neuroserpin inclusions and inflammatory responses. The changes were accompanied by a transient increase in expression of Xbp1 spliced at 45 weeks and increased ERdJ4 mRNAs at 80 weeks. The sequestration of UPR activators GRP78 and GRP94 in neuroserpin inclusions might explain the limited UPR responses despite the accumulation of neuroserpin in the ER in this FENIB mouse model.

Subject

Epilèpsia, Genètica, Sistema nerviós, Inflamació, Neuropèptids

Subject (English)

Epilepsy, Genetics, Nervous system, Inflammation, Neuropeptides

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Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citation

LÓPEZ GONZÁLEZ, Irene, et al. Limited unfolded protein response and inflammation in neuroserpinopathy. Journal of Neuropathology and Experimental Neurology. 2016. Vol. 75, num. 2, pags. 121-131. ISSN 0022-3069. [consulted: 9 of August of 2026]. Available at: https://hdl.handle.net/2445/148464

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