NOTCH2NLC GGC intermediate repeat with serine induces hypermyelination and early Parkinson’s disease-like phenotypes in mice
Our in vitro and in vivo investigations provide the first evidence that the N2C-GGC intermediate repeat with serine promotes intranuclear aggregation of N2C, leading to mitochondrial dysfunction-associated hypermyelination and neuronal hyperexcitability. These changes contribute to motor deficits in early PD-like neurodegeneration in NREDs.
Authors
- Brijesh Kumar Singh (ORCID: https://orcid.org/0000-0002-9689-8382)
- Haitao Tu (ORCID: https://orcid.org/0000-0001-7499-0682)
- Jayne Yi Tan
- Xin Yi Yeo (ORCID: https://orcid.org/0000-0003-1546-4564)
- Adeline Su Lyn Ng (ORCID: https://orcid.org/0000-0001-8822-8496)
- Eng‐King Tan (ORCID: https://orcid.org/0000-0003-2977-9743)
- Isabelle Bonne (ORCID: https://orcid.org/0000-0002-8261-6794)
- Li Zeng (ORCID: https://orcid.org/0000-0003-3242-2286)
- Zhidong Zhou (ORCID: https://orcid.org/0000-0003-0251-4163)
- Sangyong Jung (ORCID: https://orcid.org/0000-0003-3017-1145)
- Shuo‐Chien Ling (ORCID: https://orcid.org/0000-0002-0300-8812)
- Zhi-Wei Zhang
- Chi Li (ORCID: https://orcid.org/0000-0002-8424-9721)
- Zhihong Li (ORCID: https://orcid.org/0000-0003-1548-8996)
- Wei Zhou (ORCID: https://orcid.org/0000-0002-3139-989X)
- Sook‐Yoong Chia
- Aik Yong Sim
- Dongrui Ma
Institutions
- SingHealth (SG)
- National University of Singapore (SG)
- Nanyang Technological University (SG)
- Singapore General Hospital (SG)
- SingHealth Duke-NUS Academic Medical Centre (SG)
- Duke-NUS Medical School (SG)
- National Neuroscience Institute (SG)
- Stomatology Hospital (CN)
- CHA University (KR)
Publication Details
- Journal
- Molecular Neurodegeneration
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1186/s13024-024-00780-2
- Citations
- 5
- Primary Topic
- Genetic Neurodegenerative Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.34
Funders
- Duke-NUS Medical School
- Université de Strasbourg
- Medical Research Council
- National Medical Research Council