Mapping the neural and molecular basis underlying fatigue in Parkinson’s disease
Fatigue is a common and debilitating non-motor symptom in patients with Parkinson's disease (PD). By integrating the activation likelihood estimation (ALE) meta-analysis and activation network mapping (ANM) technique, the brain network underlying fatigue (referred to as "fatigue-related network") in PD was identified, comprising widespread brain regions primarily involving the somatomotor and frontoparietal networks. This network was interpreted through transcriptomic patterns, chemoarchitectures, and behavioral relevance. Fatigue-related genes were predominantly enriched in synaptic and actin filament-related biological processes and showed primary expression in neurons and oligodendrocytes. The fatigue-related network closely corresponded to the spatial distribution of acetylcholine, glutamate, and norepinephrine systems and was primarily linked to motor function. This study defines a distinct brain network substrate underlying fatigue in PD, advancing our understanding of the neurobiological mechanisms and facilitating the development of effective therapies for affected patients.
Authors
- Yuan Gao (ORCID: https://orcid.org/0000-0002-2990-9205)
- Zhi-Qin Sun (ORCID: https://orcid.org/0000-0001-8538-7360)
- Junbo Hou (ORCID: https://orcid.org/0000-0003-1281-5162)
- Jiaojian Wang (ORCID: https://orcid.org/0000-0002-0421-5709)
- Yanbing Hou (ORCID: https://orcid.org/0009-0008-2832-2577)
- Heng Shao (ORCID: https://orcid.org/0000-0003-4923-4628)
- Li Zhu (ORCID: https://orcid.org/0000-0001-5249-6536)
- Futing Yang
- Zanzong Sun
- Jun-Yi Shen (ORCID: https://orcid.org/0000-0002-2656-1856)
- Yin Mo
- Rucheng Yang
- L. C. S. Tan
Institutions
- Kunming University of Science and Technology (CN)
- Sichuan University (CN)
- Kunming Medical University (CN)
- West China Hospital of Sichuan University (CN)
- First People's Hospital of Yunnan Province (CN)
- Chongqing Vocational and Technical University of Mechatronics (CN)
- The First Hospital of Kunming (CN)
- First Affiliated Hospital of Kunming Medical University (CN)
- Hangzhou Hospital of Traditional Chinese Medicine (CN)
- Yunnan Yingmao Biotechnology (China) (CN)
- First People's Hospital of Chongqing (CN)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-11-29
- DOI
- https://doi.org/10.1038/s41531-025-01216-4
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Kunming University of Science and Technology