Polyphenols as Wnt/β-catenin pathway modulators: A promising strategy in clinical neurodegeneration

Biswajit Kumar Utpal , Sajib Chandra Roy , Mehrukh Zehravi , Sherouk Hussein Sweilam , A. Dinesh Raja , M. Akiful Haque , Chandan Nayak , Senthilkumar Balakrishnan , Laliteshwar Pratap Singh , Saswati Panigrahi , Mohammed Ali Alshehri , Safia Obaidur Rab , Najmus Sakib Minhaj , Talha Bin Emran

Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (2) : 266 -286.

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Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (2) : 266 -286. DOI: 10.1002/ame2.12525
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Polyphenols as Wnt/β-catenin pathway modulators: A promising strategy in clinical neurodegeneration

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Abstract

Polyphenols, a diverse group of naturally occurring compounds found in plants, have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases (NDs). The Wnt/β-catenin (WβC) signaling pathway, a crucial player in neurogenesis, neuronal survival, and synaptic plasticity, is involved in several cellular mechanisms related to NDs. Dysregulation of this pathway is a hallmark in the development of various NDs. This study explores multiple polyphenolic compounds, such as flavonoids, stilbenes, lignans, and phenolic acids, and their potential to protect the nervous system. It provides a comprehensive analysis of their effects on the WβC pathway, elucidating their modes of action. The study highlights the dual function of polyphenols in regulating and protecting the nervous system, providing reassurance about the research benefits. This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research, shedding light on how these substances influence the various components of the pathway. The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress, inflammation, and apoptotic processes, ultimately improving the function and survival of neurons. This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway, which could lead to the development of innovative therapeutic options for NDs.

Keywords

neurodegenerative diseases / neurological diseases / polyphenols / Wnt/β-catenin pathway

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Biswajit Kumar Utpal, Sajib Chandra Roy, Mehrukh Zehravi, Sherouk Hussein Sweilam, A. Dinesh Raja, M. Akiful Haque, Chandan Nayak, Senthilkumar Balakrishnan, Laliteshwar Pratap Singh, Saswati Panigrahi, Mohammed Ali Alshehri, Safia Obaidur Rab, Najmus Sakib Minhaj, Talha Bin Emran. Polyphenols as Wnt/β-catenin pathway modulators: A promising strategy in clinical neurodegeneration. Animal Models and Experimental Medicine, 2025, 8(2): 266-286 DOI:10.1002/ame2.12525

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