Mitochondrial rescue in Alzheimer's disease: Exploring marine-derived compounds for brain metabolism regulation.

Abstract

Alzheimer Disease (AD) is a progressive neurodegenerative condition because of its cognitive impairment, synaptic impairment and loss of neurons. Mitochondrial dysfunction has become one of the key factors of disease development and progression and one of the several pathological characteristics of AD. The mitochondrial cascade hypothesis suggests that amyloid-β and tau pathology depend on age-related mitochondrial impairment, which is an earlier and faster process and provokes neurodegeneration. Mitochondria play critical roles in metabolism of neuronal energy, maintenance of calcium and regulation of reactive oxygen species (ROS); their dysfunction leads to bioenergetic impairment, oxidative stress, and synaptic failure. Marine ecosystems constitute an unexampled source of bioactive therapeutic-related compounds of structural diversity. Marine-derived compounds (MDCs) such as polysaccharides, oligosaccharides, polyphenols, lipids, alkaloids and peptides have antioxidant, anti-inflammatory, and neuroprotective effects. Recent reports indicate that MDCs can salvage mitochondrial performance by increasing biogenesis, restoring dynamics (fusion fission balance), modulating metabolism and improving mitochondrial quality control. The compounds also control metabolism of the brain affecting the use of glucose, lipid metabolism, and synthesis of neurotransmitters. This chapter clearly discusses the insights of marine-derived compounds as a mitochondrial rescue in AD. We stress their chemical heterogeneity, biologic activity and mode of action including the regulation of signaling pathways, e.g. AMPK, PI3K/Akt, MAPK, and SIRT1. We also talk about their effects on synaptic plasticity, neuronal survival and cognitive function. Lastly, we have also find the research gaps, research challenges, and perspectives and highlight the necessity of translational research, better bioavailability, and sustainable harvesting plans. Marine-derived compounds as a group are one of the brightest prospects in AD therapeutics by providing innovative methods to restore the state of mitochondria and control the metabolism in the brain.