Secondary Metabolites from Plants Possessing Inhibitory Properties against Beta-Amyloid Aggregation as Revealed by Thioflavin-T Assay and Correlations with Investigations on Transgenic Mouse Models of Alzheimer’s Disease

Ştefănescu, Raluca; Stanciu, Gabriela Dumitriţa; Luca, Andrei; Păduraru, Luminiţa; Tamba, Bogdan Ionel

doi:10.3390/biom10060870

Cited by 23 publications

(18 citation statements)

References 107 publications

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“…SAA, an apo-lipoprotein synthesized by the liver, is an acute phase reactant extensively studied in various acute pathologies in adults (cardiac, renal, degenerative disorders) [ 80 , 81 , 82 , 83 , 84 , 85 ]. Its levels rise early during the inflammatory response up to 1000 times higher than the baseline serum values but are significantly influenced by the patient’s hepatic function and nutritional status.…”

Section: Biomarkers Commonly Used or Under Consideration For Eos Dmentioning

confidence: 99%

Relevance of Biomarkers Currently in Use or Research for Practical Diagnosis Approach of Neonatal Early-Onset Sepsis

et al. 2020

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Neonatal early-onset sepsis (EOS) is defined as an invasive infection that occurs in the first 72 h of life. The incidence of EOS varies from 0.5–2% live births in developed countries, up to 9.8% live births in low resource settings, generating a high mortality rate, especially in extremely low birth weight neonates. Clinical signs are nonspecific, leading to a late diagnosis and high mortality. Currently, there are several markers used for sepsis evaluation, such as hematological indices, acute phase reactants, cytokines, which by themselves do not show acceptable sensitivity and specificity for the diagnosis of EOS in neonates. Newer and more selective markers have surfaced recently, such as presepsin and endocan, but they are currently only in the experimental research stages. This comprehensive review article is based on the role of biomarkers currently in use or in the research phase from a basic, translational, and clinical viewpoint that helps us to improve the quality of neonatal early-onset sepsis diagnosis and management.

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Section: Biomarkers Commonly Used or Under Consideration For Eos Dmentioning

confidence: 99%

Relevance of Biomarkers Currently in Use or Research for Practical Diagnosis Approach of Neonatal Early-Onset Sepsis

et al. 2020

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“…Furthermore, compounds that inhibit the aggregation of Aβ might also be effective against tau aggregation. One such example is the aforementioned curcumin [ 237 ]. Curcumin and other secondary metabolites from plants affect Aβ aggregation, as observed by thioflavin T assay.…”

Section: Pharmacological Modulators Of Tau Aggregationmentioning

confidence: 99%

Pharmacological Modulators of Tau Aggregation and Spreading

Dominguez-Meijide

Vasili²,

Outeiro

2020

Brain Sciences

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Tauopathies are neurodegenerative disorders characterized by the deposition of aggregates composed of abnormal tau protein in the brain. Additionally, misfolded forms of tau can propagate from cell to cell and throughout the brain. This process is thought to lead to the templated misfolding of the native forms of tau, and thereby, to the formation of newer toxic aggregates, thereby propagating the disease. Therefore, modulation of the processes that lead to tau aggregation and spreading is of utmost importance in the fight against tauopathies. In recent years, several molecules have been developed for the modulation of tau aggregation and spreading. In this review, we discuss the processes of tau aggregation and spreading and highlight selected chemicals developed for the modulation of these processes, their usefulness, and putative mechanisms of action. Ultimately, a stronger understanding of the molecular mechanisms involved, and the properties of the substances developed to modulate them, will lead to the development of safer and better strategies for the treatment of tauopathies.

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“…A rich and important literature ( Ma et al, 2020 ; Muscat et al, 2020b ; Stefanescu et al, 2020 ) reports both experimental and computational studies, focused on the effects of natural compounds on different self-aggregated Aβ species. We have reviewed here those studies in which the proposed molecular mechanism of action is supported by a combination of biophysical approaches and experimental structural data.…”

Section: Introductionmentioning

confidence: 99%

Natural Compounds as Inhibitors of Aβ Peptide Aggregation: Chemical Requirements and Molecular Mechanisms

Pagano¹,

Tomaselli²,

Molinari³

et al. 2020

Front. Neurosci.

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Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, with no cure and preventive therapy. Misfolding and extracellular aggregation of Amyloid-β (Aβ) peptides are recognized as the main cause of AD progression, leading to the formation of toxic Aβ oligomers and to the deposition of β-amyloid plaques in the brain, representing the hallmarks of AD. Given the urgent need to provide alternative therapies, natural products serve as vital resources for novel drugs. In recent years, several natural compounds with different chemical structures, such as polyphenols, alkaloids, terpenes, flavonoids, tannins, saponins and vitamins from plants have received attention for their role against the neurodegenerative pathological processes. However, only for a small subset of them experimental evidences are provided on their mechanism of action. This review focuses on those natural compounds shown to interfere with Aβ aggregation by direct interaction with Aβ peptide and whose inhibitory mechanism has been investigated by means of biophysical and structural biology experimental approaches. In few cases, the combination of approaches offering a macroscopic characterization of the oligomers, such as TEM, AFM, fluorescence, together with high-resolution methods could shed light on the complex mechanism of inhibition. In particular, solution NMR spectroscopy, through peptide-based and ligand-based observation, was successfully employed to investigate the interactions of the natural compounds with both soluble NMR-visible (monomer and low molecular weight oligomers) and NMR-invisible (high molecular weight oligomers and protofibrils) species. The molecular determinants of the interaction of promising natural compounds are here compared to infer the chemical requirements of the inhibitors and the common mechanisms of inhibition. Most of the data converge to indicate that the Aβ regions relevant to perturb the aggregation cascade and regulate the toxicity of the stabilized oligomers, are the N-term and β1 region. The ability of the natural aggregation inhibitors to cross the brain blood barrier, together with the tactics to improve their low bioavailability are discussed. The analysis of the data ensemble can provide a rationale for the selection of natural compounds as molecular scaffolds for the design of new therapeutic strategies against the progression of early and late stages of AD.

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Secondary Metabolites from Plants Possessing Inhibitory Properties against Beta-Amyloid Aggregation as Revealed by Thioflavin-T Assay and Correlations with Investigations on Transgenic Mouse Models of Alzheimer’s Disease

Cited by 23 publications

References 107 publications

Relevance of Biomarkers Currently in Use or Research for Practical Diagnosis Approach of Neonatal Early-Onset Sepsis

Relevance of Biomarkers Currently in Use or Research for Practical Diagnosis Approach of Neonatal Early-Onset Sepsis

Pharmacological Modulators of Tau Aggregation and Spreading

Natural Compounds as Inhibitors of Aβ Peptide Aggregation: Chemical Requirements and Molecular Mechanisms

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