Abstract
Alzheimer’s disease (AD) is an irreversible and progressive brain disorder that slowly destroys memory and thinking skills, and, eventually, the ability to perform simple tasks. As the aging population continues to increase exponentially, AD has become a big concern for society. Therefore, neuroprotective compounds are in the spotlight, as a means to tackle this problem. On the other hand, since it is believed—in many cultures—that marine organisms in an individual diet cannot only improve brain functioning, but also slow down its dysfunction, many researchers have focused on identifying neuroprotective compounds from marine resources. The fact that the marine environment is a rich source of structurally unique and biologically and pharmacologically active compounds, with unprecedented mechanisms of action, marine macroorganisms, such as tunicates, corals, sponges, algae, as well as microorganisms, such as marine-derived bacteria, actinomycetes, and fungi, have been the target sources of these compounds. Therefore, this literature review summarizes and categorizes various classes of marine-derived compounds that are able to inhibit key enzymes involved in AD, including acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-secretase (BACE-1), and different kinases, together with the related pathways involved in the pathogenesis of AD. The compounds discussed herein are emerging as promising anti-AD activities for further in-depth in vitro and in vivo investigations, to gain more insight of their mechanisms of action and for the development of potential anti-AD drug leads.
Highlights
Alzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disorder affecting more than 50 million people across the world [1]
2-Amino-3,9-dimethyl-5-methylamino-3H-1,3,4,6-tetrazacyclopent[e]azulene (140), a pseudozoanthoxanthin from an unidentified Caribbean zoanthid, and the bromopyrrole alkaloid, stevensine (141) (Figure 10), recovered from a marine sponge A. verrucosa, which was collected in the Gulf of Naples, were found to inhibit the murine BACE-1 with IC50 values of 0.9 and 1.4 μM, respectively
They have found that 170–172 decreased both intra- and extracellular Aβ levels and tau hyperphosphorylation via modulation of N-methyl-D-aspartate (NMDA) receptors that is possibly secondary to voltage-gated potassium (Kv ) channel inhibition in an in vitro mouse model of AD [95]
Summary
Alzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disorder affecting more than 50 million people across the world [1]. Kabir et al and Martins et al have reviewed various marine natural products, i.e., DHA (1), bryostatin-1 (4), anabaseine (5), homotaurine (6), and its derivatives, rifampicin (7), anhydroexfoliamycin (8), undecylprodigioisin (9), GV-971 (10), 13-desmethyl spirolide C (11), and dictyostatin (12), which have successfully passed the preclinical or clinical trials phases. These marine compounds show a well-tolerated behavior in AD individuals with no significant drug-associated side effects (Figure 1) [21,22]. In order to facilitate a readability, the compounds discussed are grouped according to their chemical classes
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