A personalised and comprehensive approach is required to suppress or replenish SNCA for Parkinson’s disease

Dunhui Li; Wai Yan Yau; Shengdi Chen; Steve Wilton; Frank Mastaglia

doi:10.1038/s41531-025-00887-3

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A personalised and comprehensive approach is required to suppress or replenish SNCA for Parkinson’s disease

Journal article

Open access

Peer reviewed

A personalised and comprehensive approach is required to suppress or replenish SNCA for Parkinson’s disease

Dunhui Li, Wai Yan Yau, Shengdi Chen, Steve Wilton and Frank Mastaglia

NPJ Parkinson's Disease, Vol.11(1), 42

2025

DOI: https://doi.org/10.1038/s41531-025-00887-3

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Abstract

631/378/1689/1718

631/80

Biomedical and Life Sciences

Biomedicine

General

Neurology

Neurosciences

Perspective

Based on the prevailing α-synuclein “gain-of-function” hypothesis, reducing α-synuclein levels and removing its aggregates is a current focus of disease-modifying therapies for Parkinson’s disease. Emerging evidence of α-synuclein “loss-of-function” suggests that it may be necessary to replenish monomeric α-synuclein levels. We propose a personalized and comprehensive approach for different Parkinson’s subgroups based on whether α-synuclein is likely to contribute to disease pathogenesis through a “gain-of-function”, “loss-of-function”, or both mechanisms.

Details

Title: A personalised and comprehensive approach is required to suppress or replenish SNCA for Parkinson’s disease
Authors/Creators: Dunhui Li - Murdoch University, Centre for Molecular Medicine and Innovative Therapeutics
Wai Yan Yau - Perron Institute for Neurological and Translational Science
Shengdi Chen - Ruijin Hospital
Steve Wilton - Murdoch University, Centre for Molecular Medicine and Innovative Therapeutics
Frank Mastaglia - Perron Institute for Neurological and Translational Science
Publication Details: NPJ Parkinson's Disease, Vol.11(1), 42
Publisher: Nature Publishing Group UK
Number of pages: 8
Grant note: Bryant Stokes Neurological Research FundChannel 7 Telethon Trust Research Fund
We would like to thank Professor Anthony E. Lang (Department of Medicine, Division of Neurology, University of Toronto) for his helpful review and constructive comments for this manuscript. Dr Li received salary support from the philanthropic Giumelli Family Foundation and receives research grants from Bryant Stokes Neurological Research Fund and Channel 7 Telethon Trust Research Fund. No other disclosures to report.
Identifiers: 991005750230207891
Murdoch Affiliation: Personalised Medicine Centre; Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.67 Parkinson's Disease
Web Of Science research areas: Neurosciences
ESI research areas: Neuroscience & Behavior