• Spandana Rajendra Kopalli, Tapan Behl, Ashishkumar Kyada, M M Rekha, Mayank Kundlas, Pooja Rani, Deepak Nathiya, Satyam NaiduKKDepartment of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh 531162, India., Monica Gulati, Manish Bhise, Priyanka Gupta, Pranay Wal, Mohammad Fareed, Seema Ramniwas, Sushruta Koppula, and Amin Gasmi.
• Department of Bioscience and Biotechnology, Sejong University, Gwangjin-gu, Seoul 05006 Republic of Korea.
• Neuroscience. 2025 Feb 6.

AbstractFlavonoids are a broad family of polyphenolic chemicals that are present in a wide variety of fruits, vegetables, and medicinal plants. Because of their neuroprotective qualities, flavonoids have attracted a lot of interest. The potential of flavonoids to control synaptic plasticity-a crucial process underlying memory, learning, and cognitive function-is becoming more and more clear. Dysregulation of synaptic plasticity is a feature of neurodegenerative diseases such as amyotrophic lateral sclerosis (0.4 %), Parkinson's (1-2 %), Alzheimer's (5-7 %), and Huntington's ((0.2 %)). This review discusses the molecular mechanisms via which flavonoids influence synaptic plasticity as well as their therapeutic potential in neurodegenerative diseases. Flavonoids modulate key signaling pathways such as MAPK/ERK and PI3K/Akt/mTOR to support neuroprotection, synaptic plasticity, and neuronal health, while also influencing neurotrophic factors (BDNF, NGF) and their receptors (TrkB, TrkA). They regulate neurotransmitter receptors like GABA, AMPA, and NMDA to balance excitatory and inhibitory transmission, and exert antioxidant effects via the Nrf2-ARE pathway and anti-inflammatory actions by inhibiting NF-κB signaling, highlighting their potential for treating neurodegenerative diseases. These varied reactions support the preservation of synapse function and neuronal integrity in the face of neurodegenerative insults. Flavonoids can reduce the symptoms of neurodegeneration, prevent synaptic loss, and enhance cognitive function, according to experimental studies. However, there are still obstacles to using these findings in clinical settings, such as limited bioavailability and the need for consistent dose. The focus of future research should be on improving flavonoid delivery systems and combining them with conventional medications.Copyright © 2025. Published by Elsevier Inc.

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