Repurposing the memory-promoting meclofenoxate hydrochloride as a treatment for Parkinson’s disease through integrative multi-omics analysis

Zhang, Huasong, Fan, Cong, Li, Ling, Liu, Feiyi, Li, Shaoying, Ma, Linyun, Yang, Yuanhao, Cooper, David N. ORCID: https://orcid.org/0000-0002-8943-8484, Yang, Yuedong, Hu, Ronggui and Zhao, Huiying 2025. Repurposing the memory-promoting meclofenoxate hydrochloride as a treatment for Parkinson’s disease through integrative multi-omics analysis. npj Parkinson's Disease 11 (1) , 167. 10.1038/s41531-025-01027-7

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Abstract

Parkinson’s disease (PD) is a devastating neurodegenerative disorder with growing prevalence worldwide and, as yet, no effective treatment. Drug repurposing is invaluable for detecting novel PD therapeutics. Here, we compiled gene expression data from 1231 healthy human brain samples and 357 samples across tissues, ethnicities, brain regions, Braak stages, and disease status. By integrating them with multiple-source genomic data, we found a PD-associated gene co-expression module, and its alignment with the CMAP database successfully identified drug candidates. Among these, meclofenoxate hydrochloride (MH) and sodium phenylbutyrate (SP) are indicated to be able to prevent mitochondrial destruction, reduce lipid peroxidation, and protect dopamine synthesis. MH was validated to prevent neuronal death and synaptic damage, improve motor function, and reduce anhedonic and depressive-like behaviors of PD mice. The interaction of MH with a PD-related protein, sigma1, was confirmed experimentally. Thus, our findings support that MH potentially ameliorates PD by interacting with sigma1.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/, Type: open-access
Publisher:	Nature Research
Date of First Compliant Deposit:	18 June 2025
Date of Acceptance:	28 May 2025
Last Modified:	18 Jun 2025 09:15
URI:	https://orca.cardiff.ac.uk/id/eprint/179144

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