Marine Drugs

Research

Jump to: Review

20 pages, 4367 KiB

Open AccessArticle

Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease β Secretase, BACE1

by Courtney J. Mycroft-West, Anthony J. Devlin, Lynsay C. Cooper, Scott E. Guimond, Patricia Procter, Marco Guerrini, Gavin J. Miller, David G. Fernig, Edwin A. Yates, Marcelo A. Lima and Mark A. Skidmore

Mar. Drugs 2021, 19(4), 203; https://doi.org/10.3390/md19040203 - 3 Apr 2021

Cited by 11 | Viewed by 4018

Abstract

Only palliative therapeutic options exist for the treatment of Alzheimer’s Disease; no new successful drug candidates have been developed in over 15 years. The widely used clinical anticoagulant heparin has been reported to exert beneficial effects through multiple pathophysiological pathways involved in the [...] Read more.

Only palliative therapeutic options exist for the treatment of Alzheimer’s Disease; no new successful drug candidates have been developed in over 15 years. The widely used clinical anticoagulant heparin has been reported to exert beneficial effects through multiple pathophysiological pathways involved in the aetiology of Alzheimer’s Disease, for example, amyloid peptide production and clearance, tau phosphorylation, inflammation and oxidative stress. Despite the therapeutic potential of heparin as a multi-target drug for Alzheimer’s disease, the repurposing of pharmaceutical heparin is proscribed owing to the potent anticoagulant activity of this drug. Here, a heterogenous non-anticoagulant glycosaminoglycan extract, obtained from the shrimp Litopenaeus vannamei, was found to inhibit the key neuronal β-secretase, BACE1, displaying a more favorable therapeutic ratio compared to pharmaceutical heparin when anticoagulant activity is considered. Full article

(This article belongs to the Special Issue Anti-Alzheimer Agents from Marine Sources)

► Show Figures

Graphical abstract

Review

Jump to: Research

25 pages, 2967 KiB

Open AccessReview

Application of Marine Natural Products against Alzheimer’s Disease: Past, Present and Future

by Di Hu, Yating Jin, Xiangqi Hou, Yinlong Zhu, Danting Chen, Jingjing Tai, Qianqian Chen, Cui Shi, Jing Ye, Mengxu Wu, Hong Zhang and Yanbin Lu

Mar. Drugs 2023, 21(1), 43; https://doi.org/10.3390/md21010043 - 5 Jan 2023

Cited by 14 | Viewed by 6354

Abstract

Alzheimer’s disease (AD), a neurodegenerative disease, is one of the most intractable illnesses which affects the elderly. Clinically manifested as various impairments in memory, language, cognition, visuospatial skills, executive function, etc., the symptoms gradually aggravated over time. The drugs currently used clinically can [...] Read more.

Alzheimer’s disease (AD), a neurodegenerative disease, is one of the most intractable illnesses which affects the elderly. Clinically manifested as various impairments in memory, language, cognition, visuospatial skills, executive function, etc., the symptoms gradually aggravated over time. The drugs currently used clinically can slow down the deterioration of AD and relieve symptoms but cannot completely cure them. The drugs are mainly acetylcholinesterase inhibitors (AChEI) and non-competitive N-methyl-D-aspartate receptor (NDMAR) antagonists. The pathogenesis of AD is inconclusive, but it is often associated with the expression of beta-amyloid. Abnormal deposition of amyloid and hyperphosphorylation of tau protein in the brain have been key targets for past, current, and future drug development for the disease. At present, researchers are paying more and more attention to excavate natural compounds which can be effective against Alzheimer’s disease and other neurodegenerative pathologies. Marine natural products have been demonstrated to be the most prospective candidates of these compounds, and some have presented significant neuroprotection functions. Consequently, we intend to describe the potential effect of bioactive compounds derived from marine organisms, including polysaccharides, carotenoids, polyphenols, sterols and alkaloids as drug candidates, to further discover novel and efficacious drug compounds which are effective against AD. Full article

(This article belongs to the Special Issue Anti-Alzheimer Agents from Marine Sources)

► Show Figures

Graphical abstract

20 pages, 1960 KiB

Open AccessReview

Marine Sources of DHA-Rich Phospholipids with Anti-Alzheimer Effect

by Inês Ferreira, Amélia P. Rauter and Narcisa M. Bandarra

Mar. Drugs 2022, 20(11), 662; https://doi.org/10.3390/md20110662 - 25 Oct 2022

Cited by 18 | Viewed by 4318

Abstract

Alzheimer’s disease (AD) is a complex and progressive disease, which affects millions of people around the world. Despite the many efforts over the years to find efficient therapeutics, there is no cure yet. Nonetheless, many compounds have been proven to decrease Alzheimer’s symptoms. [...] Read more.

Alzheimer’s disease (AD) is a complex and progressive disease, which affects millions of people around the world. Despite the many efforts over the years to find efficient therapeutics, there is no cure yet. Nonetheless, many compounds have been proven to decrease Alzheimer’s symptoms. After a short overview of the hypotheses considered in AD drug development and the drugs approved for AD treatment, which lead to symptom release, we focus on the valorization of natural marine sources that decrease AD symptoms, particularly on docosahexaenoic acid (DHA), an important component in membrane phospholipids and the most abundant n−3 polyunsaturated fatty acids (PUFA) found in gray matter of the brain and in retina and on the DHA-containing phospholipids (DHA-PLs) present in marine sources, namely fish, krill, mollusks and in fisheries and aquaculture by-products. DHA-PLs’ bioactivities are presented, namely their properties in anti-neurodegeneration, neuroinflammation, as anticancer agents, as well as their benefits to obesity and visual problems. Fisheries and aquaculture by-products are also highlighted as they have a high content of DHA and DHA-rich phospholipids, can be extracted by green methodologies and should be considered in a circular economy for a healthy sustainable future. Full article

(This article belongs to the Special Issue Anti-Alzheimer Agents from Marine Sources)

► Show Figures

Figure 1

17 pages, 2454 KiB

Open AccessReview

Alzheimer’s Disease and Toxins Produced by Marine Dinoflagellates: An Issue to Explore

by Maria João Botelho, Jelena Milinovic, Narcisa M. Bandarra and Carlos Vale

Mar. Drugs 2022, 20(4), 253; https://doi.org/10.3390/md20040253 - 2 Apr 2022

Cited by 6 | Viewed by 4031

Abstract

This paper examined the toxins naturally produced by marine dinoflagellates and their effects on increases in β-amyloid plaques along with tau protein hyperphosphorylation, both major drivers of Alzheimer’s disease (AD). This approach is in line with the demand for certain natural compounds, namely [...] Read more.

This paper examined the toxins naturally produced by marine dinoflagellates and their effects on increases in β-amyloid plaques along with tau protein hyperphosphorylation, both major drivers of Alzheimer’s disease (AD). This approach is in line with the demand for certain natural compounds, namely those produced by marine invertebrates that have the potential to be used in the treatment of AD. Current advances in AD treatment are discussed as well as the main factors that potentially affect the puzzling global AD pattern. This study focused on yessotoxins (YTXs), gymnodimine (GYM), spirolides (SPXs), and gambierol, all toxins that have been shown to reduce β-amyloid plaques and tau hyperphosphorylation, thus preventing the neuronal or synaptic dysfunction that ultimately causes the cell death associated with AD (or other neurodegenerative diseases). Another group of toxins described, okadaic acid (OA) and its derivatives, inhibit protein phosphatase activity, which facilitates the presence of phosphorylated tau proteins. A few studies have used OA to trigger AD in zebrafish, providing an opportunity to test in vivo the effectiveness of new drugs in treating or attenuating AD. Constraints on the production of marine toxins for use in these tests have been considered. Different lines of research are anticipated regarding the action of the two groups of toxins. Full article

(This article belongs to the Special Issue Anti-Alzheimer Agents from Marine Sources)

► Show Figures

Figure 1

26 pages, 5696 KiB

Open AccessReview

Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents

by Elisabete Lima and Jorge Medeiros

Mar. Drugs 2022, 20(1), 75; https://doi.org/10.3390/md20010075 - 15 Jan 2022

Cited by 15 | Viewed by 4177

Abstract

The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), increases continuously demanding the urgent development of anti-Alzheimer’s agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, [...] Read more.

The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), increases continuously demanding the urgent development of anti-Alzheimer’s agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, such as akaloids, to defend themselves. Therefore, the identification of marine natural products with neuroprotective effects is a necessity. Being that AD is not only a genetic but also an environmental complex disease, a treatment for AD remains to discover. As the major clinical indications (CI) of AD are extracellular plaques formed by β-amyloid (Aβ) protein, intracellular neurofibrillary tangles (NFTs) formed by hyper phosphorylated τ-protein, uncommon inflammatory response and neuron apoptosis and death caused by oxidative stress, alkaloids that may decrease CI, might be used against AD. Most of the alkalolids with those properties are derivatives of the amino acid tryptophan mainly with a planar indole scaffold. Certainly, alkaloids targeting more than one CI, multitarget-directed ligands (MTDL), have the potential to become a lead in AD treatment. Alkaloids to have a maximum of activity against CI, should be planar and contain halogens and amine quaternization. Full article

(This article belongs to the Special Issue Anti-Alzheimer Agents from Marine Sources)

► Show Figures

Figure 1

34 pages, 4138 KiB

Open AccessReview

Marine-Derived Compounds with Anti-Alzheimer’s Disease Activities

by Salar Hafez Ghoran and Anake Kijjoa

Mar. Drugs 2021, 19(8), 410; https://doi.org/10.3390/md19080410 - 24 Jul 2021

Cited by 25 | Viewed by 5266

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Anti-Alzheimer Agents from Marine Sources)

► Show Figures

Graphical abstract

18 pages, 889 KiB

Open AccessReview

Anti-Alzheimer’s Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential

by Md. Tanvir Kabir, Md. Sahab Uddin, Philippe Jeandet, Talha Bin Emran, Saikat Mitra, Ghadeer M. Albadrani, Amany A. Sayed, Mohamed M. Abdel-Daim and Jesus Simal-Gandara

Mar. Drugs 2021, 19(5), 251; https://doi.org/10.3390/md19050251 - 28 Apr 2021

Cited by 41 | Viewed by 7033

Abstract

Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the most common cause of dementia. It has been confirmed that the pathological processes that intervene in AD development are linked with oxidative damage to neurons, neuroinflammation, tau phosphorylation, amyloid beta (Aβ) aggregation, glutamate [...] Read more.

Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the most common cause of dementia. It has been confirmed that the pathological processes that intervene in AD development are linked with oxidative damage to neurons, neuroinflammation, tau phosphorylation, amyloid beta (Aβ) aggregation, glutamate excitotoxicity, and cholinergic deficit. Still, there is no available therapy that can cure AD. Available therapies only manage some of the AD symptoms at the early stages of AD. Various studies have revealed that bioactive compounds derived from marine organisms and plants can exert neuroprotective activities with fewer adverse events, as compared with synthetic drugs. Furthermore, marine organisms have been identified as a source of novel compounds with therapeutic potential. Thus, there is a growing interest regarding bioactive compounds derived from marine sources that have anti-AD potentials. Various marine drugs including bryostatin-1, homotaurine, anabaseine and its derivative, rifampicins, anhydroexfoliamycin, undecylprodigioisin, gracilins, 13-desmethyl spirolide-C, and dictyostatin displayed excellent bioavailability and efficacy against AD. Most of these marine drugs were found to be well-tolerated in AD patients, along with no significant drug-associated adverse events. In this review, we focus on the drugs derived from marine life that can be useful in AD treatment and also summarize the therapeutic agents that are currently used to treat AD. Full article

(This article belongs to the Special Issue Anti-Alzheimer Agents from Marine Sources)

► Show Figures

Figure 1

19 pages, 18510 KiB

Open AccessReview

Prospects of Marine Sterols against Pathobiology of Alzheimer’s Disease: Pharmacological Insights and Technological Advances

by Md. Ataur Rahman, Raju Dash, Abdullah Al Mamun Sohag, Mahboob Alam, Hyewhon Rhim, Hunjoo Ha, Il Soo Moon, Md Jamal Uddin and Md. Abdul Hannan

Mar. Drugs 2021, 19(3), 167; https://doi.org/10.3390/md19030167 - 20 Mar 2021

Cited by 19 | Viewed by 4589

Abstract

Alzheimer’s disease (AD) is a degenerative brain disorder characterized by a progressive decline in memory and cognition, mostly affecting the elderly. Numerous functional bioactives have been reported in marine organisms, and anti-Alzheimer’s agents derived from marine resources have gained attention as a promising [...] Read more.

Alzheimer’s disease (AD) is a degenerative brain disorder characterized by a progressive decline in memory and cognition, mostly affecting the elderly. Numerous functional bioactives have been reported in marine organisms, and anti-Alzheimer’s agents derived from marine resources have gained attention as a promising approach to treat AD pathogenesis. Marine sterols have been investigated for several health benefits, including anti-cancer, anti-obesity, anti-diabetes, anti-aging, and anti-Alzheimer’s activities, owing to their anti-inflammatory and antioxidant properties. Marine sterols interact with various proteins and enzymes participating via diverse cellular systems such as apoptosis, the antioxidant defense system, immune response, and cholesterol homeostasis. Here, we briefly overview the potential of marine sterols against the pathology of AD and provide an insight into their pharmacological mechanisms. We also highlight technological advances that may lead to the potential application of marine sterols in the prevention and therapy of AD. Full article

(This article belongs to the Special Issue Anti-Alzheimer Agents from Marine Sources)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Anti-Alzheimer Agents from Marine Sources

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI