Marine-Derived Compounds Show Promise for Mitochondrial Rescue in Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by cognitive impairment, synaptic dysfunction, and neuronal loss. Current therapies offer only symptomatic relief, failing to halt disease progression. Mitochondrial dysfunction is a key pathological hallmark, driving bioenergetic impairment, oxidative stress, and synaptic failure, which are upstream of amyloid-β and tau pathologies. Marine ecosystems offer a rich, underexplored source of structurally diverse bioactive compounds with potential neuroprotective effects, addressing this critical therapeutic gap.

This chapter comprehensively reviewed existing literature on marine-derived compounds (MDCs) as a strategy for mitochondrial rescue in Alzheimer's disease. Researchers discussed the chemical heterogeneity, biological activity, and diverse modes of action of MDCs, including polysaccharides, oligosaccharides, polyphenols, lipids, alkaloids, and peptides. The review focused on their impact on mitochondrial performance, brain metabolism, synaptic plasticity, neuronal survival, and cognitive function, also identifying critical research gaps and future perspectives.

Marine-derived compounds (MDCs) exhibit significant antioxidant, anti-inflammatory, and neuroprotective properties relevant to Alzheimer's disease. They were found to salvage mitochondrial performance by increasing mitochondrial biogenesis, restoring mitochondrial dynamics (fusion-fission balance), modulating mitochondrial metabolism, and improving overall mitochondrial quality control. MDCs also regulate brain metabolism by affecting glucose utilization, lipid metabolism, and neurotransmitter synthesis. Mechanistically, these compounds modulate crucial signaling pathways, including AMPK, PI3K/Akt, MAPK, and SIRT1, which are vital for cellular energy homeostasis and stress response. These actions collectively contribute to enhanced synaptic plasticity, improved neuronal survival, and better cognitive function in preclinical models.

Marine-derived compounds enhance mitochondrial function by boosting biogenesis, restoring dynamics, and improving quality control, alongside regulating key pathways like AMPK and SIRT1.