Targeting neuroinflammatory networks with marine natural products: evidence, mechanisms, and translational challenges

Neuroinflammation is a common feature of Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and traumatic brain injury (TBI). It shows a stage-dependent shift from peripheral immune involvement to more compartmentalized inflammation within the central nervous system, together with sustained glial reprogramming, amplification of inflammasome and cytokine signaling, and close coupling with metabolic stress, oxidative stress, and impaired proteostasis. In chronic disease settings, conventional peripherally acting anti-inflammatory therapies often fail to restore neuroimmune homeostasis, which supports a shift from suppressing single pathways to evaluating inflammatory network states as integrative therapeutic targets. Here, we present a narrative critical review of marine-derived bioactive compounds as multi-target, cross-system immunomodulators. Using Alzheimer’s disease as a representative mechanistic framework, we examine evidence that brown algae–derived phlorotannins, fucoxanthin, and docosahexaenoic acid (DHA) engage regulatory nodes including NF-κB/MAPK signaling, the NLRP3 inflammasome, autophagy–lysosome pathways, mitochondrial homeostasis, and synaptic plasticity. Sodium oligomannate (GV-971) is discussed as a proof-of-concept example for gut–immune–brain axis modulation, together with the interpretive limits of current mechanistic and clinical evidence. Overall, the field has substantial conceptual value, but the available evidence remains predominantly preclinical and heterogeneous. Future translation will require stage-aware stratification, route-specific development logic, translatable endpoints, and explicit PK–PD and target-engagement validation.