scholarly journals Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 347 ◽  
Author(s):  
Md. Abdul Hannan ◽  
Raju Dash ◽  
Md. Nazmul Haque ◽  
Md. Mohibbullah ◽  
Abdullah Al Mamun Sohag ◽  
...  
Keyword(s):  
Marine Algae ◽  
Brain Injuries ◽  
Protective Efficacy ◽  
Amyloid Β ◽  
Glucose Deprivation ◽  
Cholesterol Homeostasis ◽  
Bioactive Metabolites ◽  
Pharmacological Intervention ◽  
Pharmacological Mechanism ◽  
Wide Range

Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP+) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer’s disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development.

scholarly journals Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

2020 ◽  
Author(s):  
Md. Abdul Hannan ◽  
Raju Dash ◽  
Md. Nazmul Haque ◽  
Md. Mohibbullah ◽  
Abdullah Al Mamun Sohag ◽  
...  
Keyword(s):  
Marine Algae ◽  
Brain Injuries ◽  
Protective Efficacy ◽  
Glucose Deprivation ◽  
Cholesterol Homeostasis ◽  
Bioactive Metabolites ◽  
Pharmacological Intervention ◽  
Pharmacological Mechanism ◽  
Protein Clearance ◽  
Wide Range

Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP+) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer's disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development.

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

scholarly journals NLRP3 Inflammasome: A Starring Role in Amyloid-β- and Tau-Driven Pathological Events in Alzheimer’s Disease

2021 ◽  
pp. 1-22
Author(s):  
Mariana Van Zeller ◽  
Diogo M. Dias ◽  
Ana M. Sebastião ◽  
Cláudia A. Valente
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Neurofibrillary Tangles ◽  
Nlrp3 Inflammasome ◽  
Neuronal Death ◽  
Inflammatory Responses ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Wide Range

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease commonly diagnosed among the elderly population. AD is characterized by the loss of synaptic connections, neuronal death, and progressive cognitive impairment, attributed to the extracellular accumulation of senile plaques, composed by insoluble aggregates of amyloid-β (Aβ) peptides, and to the intraneuronal formation of neurofibrillary tangles shaped by hyperphosphorylated filaments of the microtubule-associated protein tau. However, evidence showed that chronic inflammatory responses, with long-lasting exacerbated release of proinflammatory cytokines by reactive glial cells, contribute to the pathophysiology of the disease. NLRP3 inflammasome (NLRP3), a cytosolic multiprotein complex sensor of a wide range of stimuli, was implicated in multiple neurological diseases, including AD. Herein, we review the most recent findings regarding the involvement of NLRP3 in the pathogenesis of AD. We address the mechanisms of NLRP3 priming and activation in glial cells by Aβ species and the potential role of neurofibrillary tangles and extracellular vesicles in disease progression. Neuronal death by NLRP3-mediated pyroptosis, driven by the interneuronal tau propagation, is also discussed. We present considerable evidence to claim that NLRP3 inhibition, is undoubtfully a potential therapeutic strategy for AD.

Age-Dependency of Total Tau in the Cerebrospinal Fluid Is Corrected by Amyloid-β 1–40: A Correlational Study in Healthy Adults

2021 ◽  
pp. 1-8
Author(s):  
Paul Theo Zebhauser ◽  
Achim Berthele ◽  
Marie-Sophie Franz ◽  
Oliver Goldhardt ◽  
Janine Diehl-Schmid ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Healthy Adults ◽  
Tau Proteins ◽  
Clinical Settings ◽  
Inclusion Criteria ◽  
Total Tau ◽  
Potential Marker ◽  
Wide Range ◽  
The Relationship

Background: Tau proteins are established biomarkers of neuroaxonal damage in a wide range of neurodegenerative conditions. Although measurement of total-Tau in the cerebrospinal fluid is widely used in research and clinical settings, the relationship between age and total-Tau in the cerebrospinal fluid is yet to be fully understood. While past studies reported a correlation between age and total-Tau in the cerebrospinal fluid of healthy adults, in clinical practice the same cut-off value is used independently of patient’s age. Objective: To further explore the relationship between age and total-Tau and to disentangle neurodegenerative from drainage-dependent effects. Methods: We analyzed cerebrospinal fluid samples of 76 carefully selected cognitively healthy adults and included amyloid-β 1–40 as a potential marker of drainage from the brain’s interstitial system. Results: We found a significant correlation of total-Tau and age, which was no longer present when correcting total-Tau for amyloid-β 1–40 concentrations. These findings were replicated under varied inclusion criteria. Conclusion: Results call into question the association of age and total-Tau in the cerebrospinal fluid. Furthermore, they suggest diagnostic utility of amyloid-β 1–40 as a possible proxy for drainage-mechanisms into the cerebrospinal fluid when interpreting biomarker concentrations for neurodegenerative diseases.

Immune modulations and immunotherapies for Alzheimer’s disease: a comprehensive review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sara Mahdiabadi ◽  
Sara Momtazmanesh ◽  
George Perry ◽  
Nima Rezaei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Cognitive Outcomes ◽  
Tau Proteins ◽  
Causal Role ◽  
Wide Range ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Immune Related Genes

Abstract Alzheimer’s disease (AD), the most common cause of dementia, is characterized by progressive cognitive and memory impairment ensued from neuronal dysfunction and eventual death. Intraneuronal deposition of tau proteins and extracellular senile amyloid-β plaques have ruled as the supreme postulations of AD for a relatively long time, and accordingly, a wide range of therapeutics, especially immunotherapies have been implemented. However, none of them resulted in significant positive cognitive outcomes. Especially, the repetitive failure of anti-amyloid therapies proves the inefficiency of the amyloid cascade hypothesis, suggesting that it is time to reconsider this hypothesis. Thus, for the time being, the focus is being shifted to neuroinflammation as a third core pathology in AD. Neuroinflammation was previously considered a result of the two aforementioned phenomena, but new studies suggest that it might play a causal role in the pathogenesis of AD. Neuroinflammation can act as a double-edged sword in the pathogenesis of AD, and the activation of glial cells is indispensable for mediating such attenuating or detrimental effects. The association of immune-related genes polymorphisms with the clinical phenotype of AD as well as the protective effect of anti-inflammatory drugs like nonsteroidal anti-inflammatory drugs supports the possible causal role of neuroinflammation in AD. Here, we comprehensively review immune-based therapeutic approaches toward AD, including monoclonal antibodies and vaccines. We also discuss their efficacy and underlying reasons for shortcomings. Lastly, we highlight the capacity of modulating the neuroimmune interactions and targeting neuroinflammation as a promising opportunity for finding optimal treatments for AD.

scholarly journals Purification, Characterization, and Antioxidant Activity of Daucosterol and Stigmasterol from Prangos ferulacea

2020 ◽  
Vol 10 (2) ◽  
pp. 2174-2180
Keyword(s):  
Antioxidant Activity ◽  
Structure Elucidation ◽  
Antiradical Activity ◽  
Bioactive Metabolites ◽  
Spectroscopic Techniques ◽  
Chromatographic Techniques ◽  
Phytochemical Investigation ◽  
Antioxidant Agents ◽  
Wide Range ◽  
Ft Ir

The genus Prangos is traditionally used for medicinal and food purposes. This genus contains a wide range of bioactive metabolites. In this work, phytochemical investigation and antioxidant activity evaluation of Prangos ferulacea were carried out. Chromatographic techniques were employed for the purification of extracts components. Spectroscopic techniques such as NMR, FT-IR, together with elemental analysis, were used for the structure elucidation of isolated compounds. Stigmasterol, daucosterol, and salicylic acid were purified and identified. Isolated compounds showed moderate to high antiradical activity in DPPH antioxidant assay. Results indicated the potential of P. ferulacea as a source of steroid and their glycosides and also its possible applications as antioxidant agents.

scholarly journals Altered plasma-type gelsolin and amyloid-β in neonates with hypoxic-ischaemic encephalopathy under therapeutic hypothermia

2018 ◽  
Vol 39 (7) ◽  
pp. 1349-1354
Author(s):  
Isabel Benavente-Fernandez ◽  
Juan J Ramos-Rodriguez ◽  
Carmen Infante-Garcia ◽  
Gema Jimenez-Gomez ◽  
Alfonso Lechuga-Sancho ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Amyloid Beta ◽  
Brain Injuries ◽  
Standard Treatment ◽  
Amyloid Β ◽  
Neonatal Deaths ◽  
Neonatal Complication ◽  
Learning Impairment ◽  
Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication responsible for ∼23% of all neonatal deaths. Also, 30–70% of these patients will suffer lifetime disabilities, including learning impairment, epilepsy or cerebral palsy. However, biomarkers for HIE screening, or monitoring disease progression are limited. Herein, we sought to evaluate the clinical usefulness of plasma-type gelsolin (pGSN) and amyloid-beta (Aβ) 40 and 42 as prognostic biomarkers for HIE. pGSN has been previously suggested as a feasible marker in other brain injuries and amyloid-beta 40 and 42 are classically assessed in neurodegenerative diseases. However, to our knowledge, they have not been previously assessed in HIE patients. We have analyzed plasma pGSN and Aβ 40 and 42 levels in 55 newborns (16 controls, 16 mild and 23 moderate-severe HIE) at birth, during 72 h of therapeutic hypothermia, a gold-standard treatment for HIE, and 24 h after hypothermia. Aβ levels were lower in HIE patients, and pGSN levels were progressively reduced in mild and moderate-severe HIE patients. The fact that pGSN reductions could predict the severity of HIE and significantly correlated with the time to undergo hypothermia supports the prognostic value of plasmatic pGSN. Further studies are warranted to investigate the role of pGSN in neonatal HIE.

Prognosis in Coma and Related Disorders of Consciousness and Mechanisms Underlying Outcomes

2019 ◽  
pp. 379-436
Author(s):  
Jerome B. Posner ◽  
Clifford B. Saper ◽  
Nicholas D. Schiff ◽  
Jan Claassen
Keyword(s):  
Brain Death ◽  
Brain Damage ◽  
Biochemical Markers ◽  
Brain Injuries ◽  
Medical Complications ◽  
Multivariate Modeling ◽  
Neurologic Injury ◽  
Wide Range ◽  
Secondary Injuries ◽  
Underlying Causes

This chapter looks at the difficulty in predicting the outcome for patients with severe brain damage. Brain death, in principle, is conceptually a single biologic state with an unequivocal future, while severe brain injuries span a wide range of outcomes depending on a number of variables that include not only the degree of neurologic injury, but also the presence and severity of medical complications. The chapter looks in detail at the process of recovery after coma. It examines the various factors that influence recovery, such as duration of coma, presence of secondary injuries, age, motor findings, biochemical markers, electrophysiological markers, and multivariate modeling. It looks at a number of underlying causes of coma and how they relate to prognosis.

scholarly journals Evaluation of Combat Helmet Behavior under Blunt Impact

2020 ◽  
Vol 10 (23) ◽  
pp. 8470
Author(s):  
Carlos Moure-Guardiola ◽  
Ignacio Rubio ◽  
Jacobo Antona-Makoshi ◽  
Álvaro Olmedo ◽  
José Antonio Loya ◽  
...  
Keyword(s):  
Brain Injuries ◽  
Linear Acceleration ◽  
Human Head ◽  
Critical Parameters ◽  
Head Model ◽  
Ballistic Impacts ◽  
Impact Surface ◽  
Blunt Impact ◽  
Wide Range ◽  
Design And Manufacture

New threats are a challenge for the design and manufacture of modern combat helmets. These helmets must satisfy a wide range of impact velocities from ballistic impacts to blunt impacts. In this paper, we analyze European Regulation ECE R22.05 using a standard surrogate head and a human head model to evaluate combat helmet performance. Two critical parameters on traumatic brain analysis are studied for different impact locations, i.e., peak linear acceleration value and head injury criterion (HIC). The results obtained are compared with different injury criteria to determine the severity level of damage induced. Furthermore, based on different impact scenarios, analyses of the influence of impact velocity and the geometry impact surface are performed. The results show that the risks associated with a blunt impact can lead to a mild traumatic brain injury at high impact velocities and some impact locations, despite satisfying the different criteria established by the ECE R22.05 standard. The results reveal that the use of a human head for the estimation of brain injuries differs slightly from the results obtained using a surrogate head. Therefore, the current combat helmet configuration must be improved for blunt impacts. Further standards should take this into account and, consequently, combat helmet manufacturers on their design process.

ORGANIC PETROLOGY OF LIPTINITES IN THE DENISON TROUGH, QUEENSLAND

1987 ◽  
Vol 27 (1) ◽  
pp. 86
Author(s):  
J.W. Beeston
Keyword(s):  
Organic Matter ◽  
Energy Storage ◽  
Marine Algae ◽  
Reproductive Organs ◽  
Coal Seams ◽  
Organic Petrology ◽  
Wide Range ◽  
Coal Facies ◽  
Abandoned Channels ◽  
Lake Margin

Liptinite macerals in the Denison Trough are derived from a wide range of organisms including marine acritarchs, and non-marine algae, lycopods, articulates, ferns and gymnosperms. They are formed from the lipid and wax-rich components of these organisms, in particular from specialised tissues, leaves and reproductive organs developed for protection and/or energy storage. They occur chiefly in terrestrially deposited sediments and coals, yet their distribution is variable amongst the seven coal facies assemblages and six disseminated organic matter (DOM) suites distinguished in the trough. The most abundant liptinites are derived from miospores, leaf cuticles and algae. Miosporinite averages 2.6 per cent of total rock and is most abundant in coal seams, banded coals and carbonaceous mudstones that were deposited in ponds, abandoned channels and intraswamp lakes, where it ranges up to 14 per cent. Cutinite averages 0.7 per cent of total rock, and is most abundant in coal seams and banded coals that were deposited as leaf banks in shallow water marginal to peat swamps, where it ranges up to 10 per cent. Alginite averages 0.1 per cent of total rock, and is most abundant in mudstones that were deposited in lake margin ponds, where it ranges up to 22 per cent. Preservation of liptinites (as determined by fluorescence) is best where they were deposited in a quiet regime, at or near their sites of origin, in concentration. In some of these situations they occur in association or juxtaposition with the highly fluorescing, non-structured macerals sporogenite, phylloresinite and fluorinite. The latter are suggested as remnants of material that has otherwise yielded oil.

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