Reversing Autophagy Inhibition Ameliorates Neurodegeneration in Hereditary Spastic Paraplegia Caused by a Degradation‐Resistant <scp> <i>SPAST</i> </scp> Mutation
Our study provides evidence linking autophagy dysfunction to SPG4 pathogenesis and demonstrates that the I344E mutation acts through a gain-of-function mechanism. These findings challenge the prevailing haploinsufficiency model and implicate autophagy modulation as a potential therapeutic strategy for SPG4 and possibly other HSPs. © 2025 International Parkinson and Movement Disorder Society.
Authors
- Jianhe Guo
- Jinhua Fan (ORCID: https://orcid.org/0000-0002-9941-7257)
- Yang Hu (ORCID: https://orcid.org/0000-0002-4508-5365)
- Min Zhong (ORCID: https://orcid.org/0000-0002-0546-9663)
- Tong‐Fei Liu (ORCID: https://orcid.org/0000-0002-3553-6871)
- Yanling Dong (ORCID: https://orcid.org/0000-0003-4356-719X)
- Dongmei Wu (ORCID: https://orcid.org/0000-0003-3148-9577)
- Yuxi Wang (ORCID: https://orcid.org/0000-0002-4056-5829)
- Lei Yang (ORCID: https://orcid.org/0000-0003-4851-8872)
- Nong Xiao (ORCID: https://orcid.org/0000-0002-6980-5013)
- Dingyi Zhang (ORCID: https://orcid.org/0000-0003-2407-0276)
- Yifan Zhang (ORCID: https://orcid.org/0009-0001-0873-3853)
Institutions
- Dalian Medical University (CN)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Ministry of Education (KR)
- Fuling Center Hospital of Chongqing (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Jiangxi Provincial Children's Hospital (CN)
- Children's Hospital of Chongqing Medical University (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Movement Disorders
- Published
- 2025-12-17
- DOI
- https://doi.org/10.1002/mds.70150
- Primary Topic
- Hereditary Neurological Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00