Signaling Pathways Triggering Therapeutical Potential of Marine-Derived Polysaccharides in Alzheimer's Disease: A...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive failure, memory impairment, and behavioral disturbances. The disease is associated with complex pathological mechanisms including amyloid-β (Aβ) plaque deposition, tau hyperphosphorylation, oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Despite extensive research, currently available therapeutic options provide only symptomatic relief and fail to halt disease progression. Consequently, increasing attention has been directed toward natural bioactive compounds with multi-target therapeutic potential. Marine ecosystems represent a vast reservoir of structurally unique biomolecules, among which marine-derived polysaccharides have emerged as promising candidates for neuroprotection. Polysaccharides such as fucoidan, alginate, carrageenan, chitosan, ulvan, chondroitin sulfate, and hyaluronic acid exhibit diverse biological activities, including antioxidant, anti-inflammatory, anti-amyloidogenic, and neuroprotective effects. These biomolecules can modulate several critical intracellular signaling pathways implicated in AD pathology, including the NF-κB, MAPK, PI3K/Akt/GSK-3β, Nrf2/ARE, STAT3, and NLRP3 inflammasome pathways. By regulating these pathways, marine polysaccharides can reduce oxidative stress, suppress neuroinflammatory responses, inhibit amyloid aggregation, attenuate tau pathology, and promote neuronal survival. Additionally, certain polysaccharides such as chitosan and alginate have demonstrated significant potential as nanocarriers for targeted drug delivery across the blood-brain barrier. This review summarizes recent advances in understanding the signaling pathways associated with AD and highlights the emerging therapeutic potential of marine-derived polysaccharides as multi-target neuroprotective agents. Overall, these marine biomolecules represent promising candidates for developing novel therapeutic strategies to mitigate neurodegeneration and improve cognitive function in Alzheimer's disease.