Parkinson’s disease (PD) has long been considered a disorder of dopamine depletion. However, dopaminergic dysfunction alone cannot explain its clinical complexity. Emerging evidence implicates non-dopaminergic systems degeneration/dysregulation as critical contributors to PD’s multifaceted pathology.
Integrating these systems into a framework of network dysfunction, this review synthesizes current knowledge on the role of non-dopaminergic systems in PD pathogenesis, symptomatology, and therapeutic advancement, advocating for a paradigm shift toward multisystem-targeted therapies. This work was supported by the National Natural Science Foundation of China (Grant No. 82201564, U23A20425). Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China The authors declare no competing interests.
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If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Beyond dopamine: the role of non-dopaminergic systems in Parkinson’s disease. npj Parkinsons Dis. (2026). https://doi.org/10.1038/s41531-026-01604-4 DOI: https://doi.org/10.1038/s41531-026-01604-4
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