Amyloid beta (Aβ) can aggregate and form plaques, which are considered as one of the major hallmarks of Alzheimer's disease. This study aims to directly compare the neuroprotective activities in vitro of two marine-derived carotenoids astaxanthin and fucoxanthin that have shown a spectrum of biological activities, including neuroprotection. The in vitro neuroprotective activities were investigated against Aβ1-42-mediated toxicity in pheochromocytoma (PC-12) neuronal cells using the MTT cell viability assay, anti-apoptotic, antioxidant and neurite outgrowth activities; as well as inhibition against Aβ1-42 fibrillization in the Thioflavin T (ThT) assay of fibril kinetics and via transmission electron microscopic (TEM) evaluation of fibril morphology. The results demonstrated that both astaxanthin and fucoxanthin exhibited multi-neuroprotective effects favouring fucoxanthin over astaxanthin supporting neuroprotective roles of marine-derived carotenoids as potential novel dementia prevention or therapeutic strategies.

This review covers the compounds isolated from marine sponges with neuroprotective activities during the period between 1999 and 2014 based on their chemical structures, collections sites, sponge taxonomy and neuroprotective effects. These compounds were isolated from marine sponges collected from 18 countries, most of them in Indonesia, followed by Japan. A total of 90 compounds were reported to exhibit a range of neuroprotective efficacy. These compounds were shown to inhibit β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), modulate the synthesis or activity of some neurotransmitters such as acetylcholinesterase and glutamate, enhancement of serotonin, reducing oxidative stress, inhibition of kinases and proteases, and enhancement of neurite growth. None of them have yet progressed into any marine pharmaceutical development pipeline, therefore sustained researches will be required to enhance the potential of utilizing these compounds in the future for prevention and therapeutic treatment of neurodegenerative diseases.

South Australia is a biodiversity hotspot of marine sponges and macroalgae. This study aimed to evaluate the potential neuroprotective activity of extracts from these two marine sources by reducing the toxicity of human amyloid beta Aβ1-42 in a cell model assay using PC-12 cells. A total of 92 extracts (43, 13, 16, and 20 extracts from sponge of 8 orders and 17 families, green algae of 3 orders and 4 families, brown algae of 6 orders and 8 families, and red algae of 5 orders and 10 families, respectively) were initially screened at three different concentrations (0.25, 2.5 and 25 μg/mL) to evaluate their toxicity using the MTT assay. About half of these extracts (26, 6, 5, and 10 extracts from sponge, green algae, brown algae, and red algae, respectively) showed some cytotoxicity, and were hence excluded from further assays. The rest of extracts (45 extracts in total) at 0.25 and 25 μg/mL were subsequently screened in a neuroprotection assay against Aβ1-42 cytotoxicity. A cell viability reduction of 30% was observed in the MTT assay when the cells were treated with 1 μM Aβ1-42. 29 extracts (13, 4, 7, and 5 extracts from sponge, green algae, brown algae, and red algae, respectively) reduced the toxicity induced by Aβ1-42 (P < 0.05), indicating neuroprotective activity. These results demonstrate that marine sponge and macroalgae form a broad spectrum are promising sources of neuroprotective compounds against the hallmark neurotoxic protein in Alzheimer's disease (AD).