Editorial

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Open AccessEditorial

Promise from the Sea

by George Perry

Mar. Drugs 2016, 14(10), 178; https://0-doi-org.brum.beds.ac.uk/10.3390/md14100178 - 09 Oct 2016

Cited by 2 | Viewed by 3996

Abstract

The twenty-first century’s greatestmedical challenge is degenerative disease. [...] Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

Research

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Open AccessArticle

Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent

by Stacee Lee Caplan, Bo Zheng, Ken Dawson-Scully, Catherine A. White and Lyndon M. West

Mar. Drugs 2016, 14(3), 55; https://0-doi-org.brum.beds.ac.uk/10.3390/md14030055 - 10 Mar 2016

Cited by 17 | Viewed by 8779

Abstract

Natural products have provided an invaluable source of inspiration in the drug discovery pipeline. The oceans are a vast source of biological and chemical diversity. Recently, this untapped resource has been gaining attention in the search for novel structures and development of new [...] Read more.

Natural products have provided an invaluable source of inspiration in the drug discovery pipeline. The oceans are a vast source of biological and chemical diversity. Recently, this untapped resource has been gaining attention in the search for novel structures and development of new classes of therapeutic agents. Pseudopterosins are group of marine diterpene glycosides that possess an array of potent biological activities in several therapeutic areas. Few studies have examined pseudopterosin effects during cellular stress and, to our knowledge, no studies have explored their ability to protect synaptic function. The present study probes pseudopterosin A (PsA) for its neuromodulatory properties during oxidative stress using the fruit fly, Drosophila melanogaster. We demonstrate that oxidative stress rapidly reduces neuronal activity, resulting in the loss of neurotransmission at a well-characterized invertebrate synapse. PsA mitigates this effect and promotes functional tolerance during oxidative stress by prolonging synaptic transmission in a mechanism that differs from scavenging activity. Furthermore, the distribution of PsA within mammalian biological tissues following single intravenous injection was investigated using a validated bioanalytical method. Comparable exposure of PsA in the mouse brain and plasma indicated good distribution of PsA in the brain, suggesting its potential as a novel neuromodulatory agent. Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

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4701 KiB

Open AccessArticle

Nitric Oxide Synthase in the Central Nervous System and Peripheral Organs of Stramonita haemastoma: Protein Distribution and Gene Expression in Response to Thermal Stress

by Mattia Toni, Federica De Angelis, Maria Carmela Bonaccorsi Di Patti and Carla Cioni

Mar. Drugs 2015, 13(11), 6636-6664; https://0-doi-org.brum.beds.ac.uk/10.3390/md13116636 - 30 Oct 2015

Cited by 7 | Viewed by 5001

Abstract

Nitric oxide (NO) is generated via the oxidation of l-arginine by the enzyme NO synthase (NOS) both in vertebrates and invertebrates. Three NOS isoforms, nNOS, iNOS and eNOS, are known in vertebrates, whereas a single NOS isoform is usually expressed in invertebrates, sharing [...] Read more.

Nitric oxide (NO) is generated via the oxidation of l-arginine by the enzyme NO synthase (NOS) both in vertebrates and invertebrates. Three NOS isoforms, nNOS, iNOS and eNOS, are known in vertebrates, whereas a single NOS isoform is usually expressed in invertebrates, sharing structural and functional characteristics with nNOS or iNOS depending on the species. The present paper is focused on the constitutive Ca²⁺/calmodulin-dependent nNOS recently sequenced by our group in the neogastropod Stramonita haemastoma (ShNOS). In this paper we provide new data on cellular distribution of ShNOS in the CNS (pedal ganglion) and peripheral organs (osphradium, tentacle, eye and foot) obtained by WB, IF, CM and NADPHd. Results demonstrated that NOS-like proteins are widely expressed in sensory receptor elements, neurons and epithelial cells. The detailed study of NOS distribution in peripheral and central neurons suggested that NOS is both intracellular and presynaptically located. Present findings confirm that NO may have a key role in the central neuronal circuits of gastropods and in sensory perception. The physiological relevance of NOS enzymes in the same organs was suggested by thermal stress experiments demonstrating that the constitutive expression of ShNOS is modulated in a time- and organ-dependent manner in response to environmental stressors. Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

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1082 KiB

Open AccessArticle

A Cultivated Form of a Red Seaweed (Chondrus crispus), Suppresses β-Amyloid-Induced Paralysis in Caenorhabditis elegans

by Jatinder Singh Sangha, Owen Wally, Arjun H. Banskota, Roumiana Stefanova, Jeff T. Hafting, Alan T. Critchley and Balakrishnan Prithiviraj

Mar. Drugs 2015, 13(10), 6407-6424; https://0-doi-org.brum.beds.ac.uk/10.3390/md13106407 - 20 Oct 2015

Cited by 17 | Viewed by 6110

Abstract

We report here the protective effects of a methanol extract from a cultivated strain of the red seaweed, Chondrus crispus, against β-amyloid-induced toxicity, in a transgenic Caenorhabditis elegans, expressing human Aβ_1-42 gene. The methanol extract of C. crispus (CCE), delayed β-amyloid-induced [...] Read more.

We report here the protective effects of a methanol extract from a cultivated strain of the red seaweed, Chondrus crispus, against β-amyloid-induced toxicity, in a transgenic Caenorhabditis elegans, expressing human Aβ_1-42 gene. The methanol extract of C. crispus (CCE), delayed β-amyloid-induced paralysis, whereas the water extract (CCW) was not effective. The CCE treatment did not affect the transcript abundance of amy1; however, Western blot analysis revealed a significant decrease of Aβ species, as compared to untreated worms. The transcript abundance of stress response genes; sod3, hsp16.2 and skn1 increased in CCE-treated worms. Bioassay guided fractionation of the CCE yielded a fraction enriched in monogalactosyl diacylglycerols (MGDG) that significantly delayed the onset of β-amyloid-induced paralysis. Taken together, these results suggested that the cultivated strain of C. crispus, whilst providing dietary nutritional value, may also have significant protective effects against β-amyloid-induced toxicity in C. elegans, partly through reduced β-amyloid species, up-regulation of stress induced genes and reduced accumulation of reactive oxygen species (ROS). Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

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Open AccessArticle

Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass

by Tatiana G. Polotow, Sandra C. Poppe, Cristina V. Vardaris, Douglas Ganini, Maísa Guariroba, Rita Mattei, Elaine Hatanaka, Maria F. Martins, Eduardo F. Bondan and Marcelo P. Barros

Mar. Drugs 2015, 13(10), 6117-6137; https://0-doi-org.brum.beds.ac.uk/10.3390/md13106117 - 28 Sep 2015

Cited by 23 | Viewed by 7884

Abstract

Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial [...] Read more.

Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions. Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

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Review

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Open AccessReview

Axonal Transport and Neurodegeneration: How Marine Drugs Can Be Used for the Development of Therapeutics

by Joseph A. White, Rupkatha Banerjee and Shermali Gunawardena

Mar. Drugs 2016, 14(5), 102; https://0-doi-org.brum.beds.ac.uk/10.3390/md14050102 - 19 May 2016

Cited by 11 | Viewed by 8905

Abstract

Unlike virtually any other cells in the human body, neurons are tasked with the unique problem of transporting important factors from sites of synthesis at the cell bodies, across enormous distances, along narrow-caliber projections, to distally located nerve terminals in order to maintain [...] Read more.

Unlike virtually any other cells in the human body, neurons are tasked with the unique problem of transporting important factors from sites of synthesis at the cell bodies, across enormous distances, along narrow-caliber projections, to distally located nerve terminals in order to maintain cell viability. As a result, axonal transport is a highly regulated process whereby necessary cargoes of all types are packaged and shipped from one end of the neuron to the other. Interruptions in this finely tuned transport have been linked to many neurodegenerative disorders including Alzheimer’s (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) suggesting that this pathway is likely perturbed early in disease progression. Therefore, developing therapeutics targeted at modifying transport defects could potentially avert disease progression. In this review, we examine a variety of potential compounds identified from marine aquatic species that affect the axonal transport pathway. These compounds have been shown to function in microtubule (MT) assembly and maintenance, motor protein control, and in the regulation of protein degradation pathways, such as the autophagy-lysosome processes, which are defective in many degenerative diseases. Therefore, marine compounds have great potential in developing effective treatment strategies aimed at early defects which, over time, will restore transport and prevent cell death. Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

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903 KiB

Open AccessFeature PaperReview

New Drugs from Marine Organisms in Alzheimer’s Disease

by Patrizia Russo, Aliaksei Kisialiou, Palma Lamonaca, Rossana Moroni, Giulia Prinzi and Massimo Fini

Mar. Drugs 2016, 14(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/md14010005 - 25 Dec 2015

Cited by 56 | Viewed by 9284

Abstract

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Current approved drugs may only ameliorate symptoms in a restricted number of patients and for a restricted period of time. Currently, there is a translational research challenge into identifying the new effective drugs and their [...] Read more.

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Current approved drugs may only ameliorate symptoms in a restricted number of patients and for a restricted period of time. Currently, there is a translational research challenge into identifying the new effective drugs and their respective new therapeutic targets in AD and other neurodegenerative disorders. In this review, selected examples of marine-derived compounds in neurodegeneration, specifically in AD field are reported. The emphasis has been done on compounds and their possible relevant biological activities. The proposed drug development paradigm and current hypotheses should be accurately investigated in the future of AD therapy directions although taking into account successful examples of such approach represented by Cytarabine, Trabectedin, Eribulin and Ziconotide. We review a complexity of the translational research for such a development of new therapies for AD. Bryostatin is a prominent candidate for the therapy of AD and other types of dementia in humans. Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

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1471 KiB

Open AccessReview

Fish Synucleins: An Update

by Mattia Toni and Carla Cioni

Mar. Drugs 2015, 13(11), 6665-6686; https://0-doi-org.brum.beds.ac.uk/10.3390/md13116665 - 30 Oct 2015

Cited by 30 | Viewed by 6131

Abstract

Synucleins (syns) are a family of proteins involved in several human neurodegenerative diseases and tumors. Since the first syn discovery in the brain of the electric ray Torpedo californica, members of the same family have been identified in all vertebrates and comparative studies [...] Read more.

Synucleins (syns) are a family of proteins involved in several human neurodegenerative diseases and tumors. Since the first syn discovery in the brain of the electric ray Torpedo californica, members of the same family have been identified in all vertebrates and comparative studies have indicated that syn proteins are evolutionary conserved. No counterparts of syns were found in invertebrates suggesting that they are vertebrate-specific proteins. Molecular studies showed that the number of syn members varies among vertebrates. Three genes encode for α-, β- and γ-syn in mammals and birds. However, a variable number of syn genes and encoded proteins is expressed or predicted in fish depending on the species. Among biologically verified sequences, four syn genes were identified in fugu, encoding for α, β and two γ (γ1 and γ2) isoforms, whereas only three genes are expressed in zebrafish, which lacks α-syn gene. The list of “non verified” sequences is much longer and is often found in sequence databases. In this review we provide an overview of published papers and known syn sequences in agnathans and fish that are likely to impact future studies in this field. Indeed, fish models may play a key role in elucidating some of the molecular mechanisms involved in physiological and pathological functions of syn proteins. Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

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Open AccessReview

Astaxanthin as a Potential Neuroprotective Agent for Neurological Diseases

by Haijian Wu, Huanjiang Niu, Anwen Shao, Cheng Wu, Brandon J. Dixon, Jianmin Zhang, Shuxu Yang and Yirong Wang

Mar. Drugs 2015, 13(9), 5750-5766; https://0-doi-org.brum.beds.ac.uk/10.3390/md13095750 - 11 Sep 2015

Cited by 144 | Viewed by 12869

Abstract

Neurological diseases, which consist of acute injuries and chronic neurodegeneration, are the leading causes of human death and disability. However, the pathophysiology of these diseases have not been fully elucidated, and effective treatments are still lacking. Astaxanthin, a member of the xanthophyll group, [...] Read more.

Neurological diseases, which consist of acute injuries and chronic neurodegeneration, are the leading causes of human death and disability. However, the pathophysiology of these diseases have not been fully elucidated, and effective treatments are still lacking. Astaxanthin, a member of the xanthophyll group, is a red-orange carotenoid with unique cell membrane actions and diverse biological activities. More importantly, there is evidence demonstrating that astaxanthin confers neuroprotective effects in experimental models of acute injuries, chronic neurodegenerative disorders, and neurological diseases. The beneficial effects of astaxanthin are linked to its oxidative, anti-inflammatory, and anti-apoptotic characteristics. In this review, we will focus on the neuroprotective properties of astaxanthin and explore the underlying mechanisms in the setting of neurological diseases. Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

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