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      Natural cholinesterase inhibitors from marine organisms

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          Abstract

          This review provides a critical and comprehensive survey of marine cholinesterase inhibitors.

          Abstract

          Covering: Published between 1974 up to 2018

          Inhibition of cholinesterases is a common approach for the management of several disease states. Most notably, cholinesterase inhibitors are used to alleviate the symptoms of neurological disorders like dementia and Alzheimer's disease and treat myasthenia gravis and glaucoma. Historically, most drugs of natural origin have been isolated from terrestrial sources and inhibitors of cholinesterases are no exception. However, the last 50 years have seen a rise in the quantity of marine natural products with close to 25 000 reported in the scientific literature. A number of marine natural products with potent cholinesterase inhibitory properties have also been reported; isolated from a variety of marine sources from algae to ascidians. Representing a diverse range of structural classes, these compounds provide inspirational leads that could aid the development of therapeutics. The current paper aims to, for the first time, comprehensively summarize the literature pertaining to cholinesterase inhibitors derived from marine sources, including the first papers published in 1974 up to 2018. The review does not report bioactive extracts, only isolated compounds, and a specific focus lies on compounds with reported dose–response data. In vivo and mechanistic data is included for compounds where this is reported. In total 185 marine cholinesterase inhibitors and selected analogs have been identified and reported and some of the compounds display inhibitory activities comparable or superior to cholinesterase inhibitors in clinical use.

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          Most cited references238

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          The cholinergic system in aging and neuronal degeneration.

          The basal forebrain cholinergic complex comprising medial septum, horizontal and vertical diagonal band of Broca, and nucleus basalis of Meynert provides the mayor cholinergic projections to the cerebral cortex and hippocampus. The cholinergic neurons of this complex have been assumed to undergo moderate degenerative changes during aging, resulting in cholinergic hypofunction that has been related to the progressing memory deficits with aging. However, the previous view of significant cholinergic cell loss during aging has been challenged. Neuronal cell loss was found predominantly in pathological aging, such as Alzheimer's disease, while normal aging is accompanied by a gradual loss of cholinergic function caused by dendritic, synaptic, and axonal degeneration as well as a decrease in trophic support. As a consequence, decrements in gene expression, impairments in intracellular signaling, and cytoskeletal transport may mediate cholinergic cell atrophy finally leading to the known age-related functional decline in the brain including aging-associated cognitive impairments. However, in pathological situations associated with cognitive deficits, such as Parkinsons's disease, Down-syndrome, progressive supranuclear palsy, Jakob-Creutzfeld disease, Korsakoff's syndrome, traumatic brain injury, significant degenerations of basal forebrain cholinergic cells have been observed. In presenile (early onset), and in the advanced stages of late-onset Alzheimer's disease (AD), a severe loss of cortical cholinergic innervation has extensively been documented. In contrast, in patients with mild cognitive impairment (MCI, a prodromal stage of AD), and early forms of AD, apparently no cholinergic neurodegeneration but a loss of cholinergic function occurs. In particular imbalances in the expression of NGF, its precursor proNGF, the high and low NGF receptors, trkA and p75NTR, respectively, changes in acetylcholine release, high-affinity choline uptake, as well as alterations in muscarinic and nicotinic acetylcholine receptor expression may contribute to the cholinergic dysfunction. These observations support the suggestion of a key role of the cholinergic system in the functional processes that lead to AD. Malfunction of the cholinergic system may be tackled pharmacologically by intervening in cholinergic as well as neurotrophic signaling cascades that have been shown to ameliorate the cholinergic deficit at early stages of the disease, and slow-down the progression. However, in contrast to many other, dementing disorders, in AD the cholinergic dysfunctions are accompanied by the occurrence of two major histopathological hallmarks such as β-amyloid plaques and neurofibrillary tangles, provoking the question whether they play a particular role in inducing or mediating cholinergic dysfunction in AD. Indeed, there is abundant evidence that β-amyloid may trigger cholinergic dysfunction through action on α7 nicotinic acetylcholine receptors, affecting NGF signaling, mediating tau phosphorylation, interacting with acetylcholinesterase, and specifically affecting the proteome in cholinergic neurons. Therefore, an early onset of an anti β-amyloid strategy may additionally be potential in preventing aging-associated cholinergic deficits and cognitive impairments. Copyright © 2010 Elsevier B.V. All rights reserved.
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            Impact of natural products on developing new anti-cancer agents.

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              Genomic insights into the marine sponge microbiome.

              Marine sponges (phylum Porifera) often contain dense and diverse microbial communities, which can constitute up to 35% of the sponge biomass. The genome of one sponge, Amphimedon queenslandica, was recently sequenced, and this has provided new insights into the origins of animal evolution. Complementary efforts to sequence the genomes of uncultivated sponge symbionts have yielded the first glimpse of how these intimate partnerships are formed. The remarkable microbial and chemical diversity of the sponge-microorganism association, coupled with its postulated antiquity, makes sponges important model systems for the study of metazoan host-microorganism interactions, and their evolution, as well as for enabling access to biotechnologically important symbiont-derived natural products. In this Review, we discuss our current understanding of the interactions between marine sponges and their microbial symbiotic consortia, and highlight recent insights into these relationships from genomic studies.
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                Author and article information

                Journal
                NPRRDF
                Natural Product Reports
                Nat. Prod. Rep.
                Royal Society of Chemistry (RSC)
                0265-0568
                1460-4752
                2019
                2019
                Affiliations
                [1 ]Department of Chemistry
                [2 ]University of Umeå
                [3 ]Umeå
                [4 ]Sweden
                [5 ]Department of Biology
                [6 ]Biotechnical Faculty
                [7 ]University of Ljubljana
                [8 ]Ljubljana
                [9 ]Slovenia
                [10 ]Institute of Preclinical Sciences
                [11 ]Veterinary Faculty
                [12 ]Department of Chemistry and Materials
                [13 ]RISE Research Institutes of Sweden
                [14 ]SE-501 15 Borås
                Article
                10.1039/C9NP00010K
                30924818
                4431079a-7030-46cd-94d2-ecb314b3d955
                © 2019

                http://rsc.li/journals-terms-of-use

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