NAR has demonstrated the ability to reduce amyloid-β plaque deposition, inhibit α-synuclein aggregation, preserve dopaminergic neurons, modulate immune responses in multiple sclerosis, and improve functional recovery after spinal cord injury.
Abstract
Neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, retinal neurodegeneration, and spinal cord injury represent a growing global health burden with limited therapeutic options. Natural compounds, particularly flavonoids, have emerged as promising neuroprotective agents. Naringenin (NAR), a citrus‐derived flavanone, exhibits potent antioxidant, anti‐inflammatory, and neuroprotective properties. Recent studies revealed that NAR modulates multiple cellular pathways, including oxidative stress reduction, mitochondrial protection, autophagy induction, inhibition of microglial activation, and suppression of neuroinflammatory signaling such as NF‐κB and NLRP3 inflammasome. Furthermore, NAR has demonstrated the ability to reduce amyloid‐β plaque deposition, inhibit α‐synuclein aggregation, preserve dopaminergic neurons, modulate immune responses in multiple sclerosis, and improve functional recovery after spinal cord injury. This review comprehensively summarizes the mechanistic insights and therapeutic potential of NAR across various neurodegenerative diseases, highlighting its promise as a multifunctional neuroprotective agent and the need for further translational research.
A narrative review evaluates the therapeutic potential of semaglutide in PD, focusing on its molecular mechanisms and preclinical and emerging clinical evidence, and suggests that semaglutide crosses the blood-brain barrier and activates GLP-1 receptors in neuronal and glial cells, reducing microglial activation, neuroinflammation, and oxidative stress while improving mitochondrial function, cellular metabolism, and neuronal survival.
Dipesh Kumar, Renuka Sahu, Naveen Kumar et al.· International Journal of Sci...· 0 citations
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, affecting millions worldwide. Despite extensive research, effective treatments remain limited. Polysaccharides, abundant biological macromolecules derived from natural resources have emerged as promising therapeutic candidates due to their antioxidant, anti-inflammatory, and neuroprotective properties. This narrative review summarizes recent preclinical and limited clinical evidence on natural polysaccharides and their structure–activity relationships (SAR) in AD. We focus on their ability to mitigate amyloid-beta (Aβ) aggregation, reduce tau hyperphosphorylation, modulate neuroinflammation, and enhance cognitive function. We emphasize novel mechanistic insights and highlight how fungal, algal, plant, and bacterial polysaccharides exert broad multi-targeted effects. Importantly, this is the first review to integrate SAR with challenges of bioavailability and blood–brain barrier (BBB) penetration, offering a framework for optimizing therapeutic design. Novel insights into the molecular mechanisms, such as activation of Nrf2 and autophagy pathways, are discussed. We also underscore the translational value of polysaccharides, noting that strategies such as structural modification, nanoparticle conjugation, and pharmacokinetic profiling could accelerate their progression toward clinical application. However, most evidence is limited to in vitro and animal models, with critical challenges including poor bioavailability, limited blood-brain barrier penetration, and a lack of standardized clinical data. We conclude that natural polysaccharides are promising, low-toxicity therapeutic agents for AD management. But for complete validation of their therapeutic potential, standardized pharmacokinetic profiling, rigorous safety assessment, and well-designed clinical trials are urgently required.
Noor Muhammad, Rui Ai, Limin Yang et al.· Frontiers in Aging Neuroscie...· 0 citations
Combined in silico and experimental findings highlight hesperidin’s strong binding to key molecular targets, whereas experimental evidence also confirms its antioxidant, anti-inflammatory, and anti-apoptotic effects, supporting its potential as a disease-modifying candidate in PD therapy.
Seyawash Ghani, Diksha Dalal, Anish Singh et al.· Current Behavioral Neuroscie...· 0 citations
A deeper understanding of aging-associated molecular dysfunction is essential to design sustainable, disease-modifying therapeutics with cross-disease relevance.
Nagaraj Rangappa, Riddhi Upadhyay, Nathish Lakshman et al.· Advances in Protein Chemistr...· 0 citations
This review consolidates current evidence regarding the mechanisms by which polyphenols modulate microglial phenotypic balance and polarization states and examines advanced delivery strategies designed to enhance their therapeutic efficacy in neuroinflammatory disorders.
