Neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's are on the rise and pose significant challenges due to the lack of effective treatments. This review critically examines the neuroprotective effects of various natural products derived from plants, marine organisms, and fungi. Natural products have long been used in traditional medicine and are gaining attention in modern drug discovery for their unique properties. The review explains how these natural products can protect neurons by influencing the key biological pathways involved in neurodegeneration. It discusses mechanisms including antioxidant effects, anti-inflammatory actions, modulation of cellular signalling, and support for mitochondrial function. A systematic literature search was conducted to minimize bias and ensure rigorous study selection. Preclinical studies using animal models and cell cultures show that secondary metabolites like polyphenols, alkaloids, and terpenoids can significantly reduce neuronal damage. Some clinical trials have shown promising results. However, challenges such as bioavailability, standardization, and dosage must be addressed to translate these findings into clinical practice. The review also evaluates the potential synergy of combining natural products with conventional treatments, offering a complementary therapeutic approach. Natural products represent a promising avenue for developing innovative treatments for neurodegenerative diseases. The review highlights key research gaps and proposes future directions. Future studies should focus on overcoming existing challenges and refining these natural products to improve their efficacy and safety in clinical settings. The application of existing knowledge has the potential to significantly enhance the quality of life for individuals affected by neurodegenerative diseases.

Centre for Natural Products Discovery School of Pharmacy and Biomolecular Sciences Liverpool John Moores University Liverpool United Kingdom

Department of Chemistry and Mathematics Al Farabi Kazakh National University Almaty Kazakhstan

Department of Pharmacognosy Faculty of Pharmacy Ankara University Ankara Türkiye

Department of Pharmacognosy Faculty of Pharmacy Medicinal Plants Research Centre Mazandaran University of Medical Sciences Sari Iran

International Joint Laboratory of Medicinal Food Development and Health Products Creation Biological Engineering Technology Innovation Center of Shandong Province Heze Branch of Qilu University of Technology Heze China

Laboratory of Advanced Theranostic Materials and Technology Ningbo Institute of Materials Technology and Engineering Chinese Academy of Sciences Ningbo China

Laboratory of Growth Regulators Palacký University and Institute of Experimental Botany The Czech Academy of Sciences Olomouc Czechia

School of Integrative Medicine and Medicinal Plants Innovation Center of Mae Fah Luang University Chiang Rai Thailand

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