Inhibition of Crmp1 Phosphorylation at Ser522 Ameliorates Motor Function and Neuronal Pathology in Amyotrophic Lateral Sclerosis Model Mice Article Swipe
Tetsuya Asano
,
Haruko Nakamura
,
Yuko Kawamoto
,
Mikiko Tada
,
Yayoi Kimura
,
Hiroshi Takano
,
Ryoji Yao
,
Hiroya Saito
,
Takuya Ikeda
,
Hiroyasu Komiya
,
Shun Kubota
,
Shunta Hashiguchi
,
Keita Takahashi
,
Misako Kunii
,
Kenichi Tanaka
,
Yoshio Goshima
,
Fumio Nakamura
,
Hideyuki Takeuchi
,
Hiroshi Doi
,
Fumiaki Tanaka
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1523/eneuro.0133-22.2022
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1523/eneuro.0133-22.2022
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder that affects upper and lower motor neurons; however, its pathomechanism has not been fully elucidated. Using a comprehensive phosphoproteomic approach, we have identified elevated phosphorylation of Collapsin response mediator protein 1 (Crmp1) at serine 522 in the lumbar spinal cord of ALS model mice overexpressing a human superoxide dismutase mutant (SOD1 G93A ). We investigated the effects of Crmp1 phosphorylation and depletion in SOD1 G93A mice using Crmp1 S522A (Ser522→Ala) knock-in ( Crmp1 k i /ki ) mice in which the S522 phosphorylation site was abolished and Crmp1 knock-out ( Crmp1 −/− ) mice, respectively. Crmp1 ki / ki / SOD1 G93A mice showed longer latency to fall in a rotarod test while Crmp1 −/− / SOD1 G93A mice showed shorter latency compared with SOD1 G93A mice. Survival was prolonged in Crmp1 ki / ki / SOD1 G93A mice but not in Crmp1 −/− / SOD1 G93A mice. In agreement with these phenotypic findings, residual motor neurons and innervated neuromuscular junctions (NMJs) were comparatively well-preserved in Crmp1 ki / ki / SOD1 G93A mice without affecting microglial and astroglial pathology. Pathway analysis of proteome alterations showed that the sirtuin signaling pathway had opposite effects in Crmp1 ki / ki / SOD1 G93A and Crmp1 −/− / SOD1 G93A mice. Our study indicates that modifying CRMP1 phosphorylation is a potential therapeutic strategy for ALS.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1523/eneuro.0133-22.2022
- https://www.eneuro.org/content/eneuro/9/3/ENEURO.0133-22.2022.full.pdf
- OA Status
- gold
- Cited By
- 8
- References
- 42
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4229002062
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4229002062Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1523/eneuro.0133-22.2022Digital Object Identifier
- Title
-
Inhibition of Crmp1 Phosphorylation at Ser522 Ameliorates Motor Function and Neuronal Pathology in Amyotrophic Lateral Sclerosis Model MiceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-05-01Full publication date if available
- Authors
-
Tetsuya Asano, Haruko Nakamura, Yuko Kawamoto, Mikiko Tada, Yayoi Kimura, Hiroshi Takano, Ryoji Yao, Hiroya Saito, Takuya Ikeda, Hiroyasu Komiya, Shun Kubota, Shunta Hashiguchi, Keita Takahashi, Misako Kunii, Kenichi Tanaka, Yoshio Goshima, Fumio Nakamura, Hideyuki Takeuchi, Hiroshi Doi, Fumiaki TanakaList of authors in order
- Landing page
-
https://doi.org/10.1523/eneuro.0133-22.2022Publisher landing page
- PDF URL
-
https://www.eneuro.org/content/eneuro/9/3/ENEURO.0133-22.2022.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.eneuro.org/content/eneuro/9/3/ENEURO.0133-22.2022.full.pdfDirect OA link when available
- Concepts
-
Amyotrophic lateral sclerosis, Phosphorylation, Neurodegeneration, Sirtuin, Neuroscience, Biology, Cell biology, Cancer research, Medicine, Internal medicine, Biochemistry, Acetylation, Gene, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
8Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 3, 2023: 1, 2022: 2Per-year citation counts (last 5 years)
- References (count)
-
42Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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