Cellular stress response and neuroprotection of flavonoids in neurodegenerative diseases: Clinical insights into targeted therapy and molecular signaling pathways

Neurodegenerative diseases (NDs) are caused by the gradual decline of neuronal structure and function, which presents significant challenges in treatment. Cellular stress responses significantly impact the pathophysiology of these disorders, often exacerbating neuronal damage. Plant-derived flavonoids have demonstrated potential as neuroprotective agents due to their potent anti-inflammatory, anti-apoptotic, and antioxidant properties. This review provides an in-depth analysis of the molecular processes and clinical insights that cause the neuroprotective properties of flavonoids in NDs. By controlling essential signaling pathways such as Nrf2/ARE, MAPK, and PI3K/Akt, flavonoids can lower cellular stress and improve neuronal survival. The study discusses the challenges of implementing these discoveries in clinical practice and emphasizes the therapeutic potential of specific flavonoids and their derivatives. Flavonoids are identified as potential therapeutic agents for NDs, potentially slowing progression by regulating cellular stress and improving neuroprotection despite their potential medicinal uses and clinical challenges. The study designed a strategy to identify literature published in prestigious journals, utilizing search results from PubMed, Scopus, and WOS. We selected and investigated original studies, review articles, and research reports published until 2024. It suggests future research and therapeutic approaches to effectively utilize the neuroprotective properties of flavonoids.