Inhibition of ER stress improves progressive motor deficits in a REEP1-null mouse model of hereditary spastic paraplegia
Hereditary spastic paraplegias (HSPs) are genetic neurodegenerative diseases. HSPs are characterized by lower-extremity weakness and spasticity. However, there is no specific clinical treatment strategy to prevent or reverse nerve degeneration in HSPs. Mutations in receptor expression-enhancing prot...
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doaj-51c73fa4625c404daf6593558dd646132021-06-02T18:43:04ZengThe Company of BiologistsBiology Open2046-63902020-09-019910.1242/bio.054296054296Inhibition of ER stress improves progressive motor deficits in a REEP1-null mouse model of hereditary spastic paraplegiaBingjie Wang0You Yu1Lai Wei2Yan Zhang3 State Key Laboratory of Membrane Biology, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China State Key Laboratory of Membrane Biology, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China State Key Laboratory of Membrane Biology, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China State Key Laboratory of Membrane Biology, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China Hereditary spastic paraplegias (HSPs) are genetic neurodegenerative diseases. HSPs are characterized by lower-extremity weakness and spasticity. However, there is no specific clinical treatment strategy to prevent or reverse nerve degeneration in HSPs. Mutations in receptor expression-enhancing protein 1 (REEP1) are well-recognized and relatively common causes of autosomal dominant HSPs. REEP1 modifies the endoplasmic reticulum (ER) shape, and is implicated in the ER stress response. Defects in the ER stress response seem to be crucial mechanisms underlying HSP neurodegeneration. Here, we report that REEP1−/− mice exhibit progressive motor deficits, along with denervation of neuromuscular junctions and increased ER stress. Moreover, marked axonal degeneration and morphological abnormalities are observed. In this study, we treated both REEP1−/− and wild-type (WT) mice with salubrinal, which is a specific inhibitor of ER stress, and we observed increased nerve-muscle connections and enhanced motor functions. Our data highlight the importance of ER homeostasis in HSPs, providing new opportunities for HSP treatment.http://bio.biologists.org/content/9/9/bio054296receptor expression-enhancing protein 1hereditary spastic paraplegiasendoplasmic reticulum stresssalubrinal |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bingjie Wang You Yu Lai Wei Yan Zhang |
spellingShingle |
Bingjie Wang You Yu Lai Wei Yan Zhang Inhibition of ER stress improves progressive motor deficits in a REEP1-null mouse model of hereditary spastic paraplegia Biology Open receptor expression-enhancing protein 1 hereditary spastic paraplegias endoplasmic reticulum stress salubrinal |
author_facet |
Bingjie Wang You Yu Lai Wei Yan Zhang |
author_sort |
Bingjie Wang |
title |
Inhibition of ER stress improves progressive motor deficits in a REEP1-null mouse model of hereditary spastic paraplegia |
title_short |
Inhibition of ER stress improves progressive motor deficits in a REEP1-null mouse model of hereditary spastic paraplegia |
title_full |
Inhibition of ER stress improves progressive motor deficits in a REEP1-null mouse model of hereditary spastic paraplegia |
title_fullStr |
Inhibition of ER stress improves progressive motor deficits in a REEP1-null mouse model of hereditary spastic paraplegia |
title_full_unstemmed |
Inhibition of ER stress improves progressive motor deficits in a REEP1-null mouse model of hereditary spastic paraplegia |
title_sort |
inhibition of er stress improves progressive motor deficits in a reep1-null mouse model of hereditary spastic paraplegia |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2020-09-01 |
description |
Hereditary spastic paraplegias (HSPs) are genetic neurodegenerative diseases. HSPs are characterized by lower-extremity weakness and spasticity. However, there is no specific clinical treatment strategy to prevent or reverse nerve degeneration in HSPs. Mutations in receptor expression-enhancing protein 1 (REEP1) are well-recognized and relatively common causes of autosomal dominant HSPs. REEP1 modifies the endoplasmic reticulum (ER) shape, and is implicated in the ER stress response. Defects in the ER stress response seem to be crucial mechanisms underlying HSP neurodegeneration. Here, we report that REEP1−/− mice exhibit progressive motor deficits, along with denervation of neuromuscular junctions and increased ER stress. Moreover, marked axonal degeneration and morphological abnormalities are observed. In this study, we treated both REEP1−/− and wild-type (WT) mice with salubrinal, which is a specific inhibitor of ER stress, and we observed increased nerve-muscle connections and enhanced motor functions. Our data highlight the importance of ER homeostasis in HSPs, providing new opportunities for HSP treatment. |
topic |
receptor expression-enhancing protein 1 hereditary spastic paraplegias endoplasmic reticulum stress salubrinal |
url |
http://bio.biologists.org/content/9/9/bio054296 |
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