Polyamines and its analogue modulates amyloid fibrillation in lysozyme: A comparative investigation

Kabir, Ayesha; Jash, Chandrima; Payghan, Pavan V.; Ghoshal, Nanda; Kumar, Gopinatha Suresh

doi:10.1016/j.bbagen.2020.129557

Cited by 9 publications

(6 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 13 In the laboratory, polyamines have been employed to promote the folding and stability of nucleic acids in vitro . 14 − 16 However, with respect to proteins, modulation of structure and/or function by polyamines has centered largely on amyloidogenesis; 17 − 19 consequently, the mechanisms by which protein structure and function can be modulated by polyamines are largely unknown.…”

mentioning

confidence: 99%

“…Mechanistically, polyamines operate on nucleic acids through interactions with the negatively charged phosphodiester backbone, resulting in changes in DNA conformation, , tRNA stabilization, and even phase separation . In the laboratory, polyamines have been employed to promote the folding and stability of nucleic acids in vitro . − However, with respect to proteins, modulation of structure and/or function by polyamines has centered largely on amyloidogenesis; − consequently, the mechanisms by which protein structure and function can be modulated by polyamines are largely unknown.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Polyamines Mediate Folding of Primordial Hyperacidic Helical Proteins

et al. 2020

View full text Add to dashboard Cite

Polyamines are known to mediate diverse biological processes, and specifically to bind and stabilize compact conformations of nucleic acids, acting as chemical chaperones that promote folding by offsetting the repulsive negative charges of the phosphodiester backbone. However, whether and how polyamines modulate the structure and function of proteins remain unclear. In particular, early proteins are thought to have been highly acidic, like nucleic acids, due to a scarcity of basic amino acids in the prebiotic context. Perhaps polyamines, the abiotic synthesis of which is simple, could have served as chemical chaperones for such primordial proteins? We replaced all lysines of an ancestral 60-residue helix-bundle protein with glutamate, resulting in a disordered protein with 21 glutamates in total. Polyamines efficiently induce folding of this hyperacidic protein at submillimolar concentrations, and their potency scaled with the number of amine groups. Compared to cations, polyamines were several orders of magnitude more potent than Na + , while Mg 2+ and Ca 2+ had an effect similar to that of a diamine, inducing folding at approximately seawater concentrations. We propose that (i) polyamines and dications may have had a role in promoting folding of early proteins devoid of basic residues and (ii) coil−helix transitions could be the basis of polyamine regulation in contemporary proteins.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Polyamines Mediate Folding of Primordial Hyperacidic Helical Proteins

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Genetic and biochemical studies have demonstrated that alternations of the Nglycan structure play crucial roles in various physiological and pathological events including progression of cancer, diabetes, and AD (Nagae et al, 2020). Lysozyme aggregation in the presence of polyamines leads to nonneuropathic amyloidosis (Kabir et al, 2020). A meta-analysis supported that the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism was associated with an increased risk of AD (Rai, 2017).…”

Section: Discussionmentioning

confidence: 99%

Effects of Qi-Fu-Yin on aging of APP/PS1 transgenic mice by regulating the intestinal microbiome

Xiao

Wang

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

IntroductionAlzheimer’s disease is the most common form of dementia and closely related to aging. Qi-Fu-Yin is widely used to treat dementia, but its anti-aging effects is unknown.MethodsWe used 11-month-old APP/PS1 transgenic mice for behavioral tests to observe the changes in cognitive function and age-related symptoms after Qi-Fu-Yin treatment. Fecal samples were collected for 16sRNA sequencing and metagenomic sequencing. Differences among the groups of intestinal microbiota and the associations with aging and intestinal microbiota were analyzed based on the results.ResultsHere we found that Qi-Fu-Yin improved the ability of motor coordination, raised survival rate and prolonged the survival days under cold stress stimulation in aged APP/ PS1 transgenic mice. Our data from 16sRNA and metagenomic sequencing showed that at the Family level, the intestinal microbiota was significantly different among wild-type mice, APP/PS1 transgenic mice and the Qi-Fu-Yin group by PCA analysis. Importantly, Qi-Fu-Yin improved the functional diversity of the major KEGG pathways, carbohydrate-active enzymes, and major virulence factors in the intestinal flora of APP/PS1 transgenic mice. Among them, the functions of eight carbohydrate-active enzymes (GT2_Glycos_transf_2, GT4, GT41, GH2, CE1, CE10, CE3, and GH24) and the functions of top three virulence factors (defensive virulence factors, offensive virulence factors and nonspecific virulence factors) were significantly and positively correlated with the level of grasping ability. We further indicated that the Qi-Fu-Yin significantly reduced the plasma levels of IL-6.ConclusionOur results indicated that the effects of Qi-Fu-Yin anti-aging of APP/PS1 transgenic mice might be through the regulation of intestinal flora diversity, species richness and the function of major active enzymes.

show abstract

“…Все они проявляют ингибирую-щее воздействие на ацетилхолинэстеразу (AChE), замедляя деградацию одного из основных нейромедиаторов -ацетилхолина, значение IС 50 заключены в пределах от 1.5 nM до 0.17µM. Кроме того, зафиксировано ингибирующее воздействие соединений 49, 50 и 53, описанных в исследовании [124], на агрегацию амилоидного белка (Aβ40), который оказывает разрушительное воздействие на нервную ткань. Отложение амилоидных агрегатов является одной из основных гипотез о механизмах возникновения болезни Альцгеймера [125,126].…”

Section: нейропротекторная активностьunclassified

Structure and biological action of analogs and derivatives of biogenic polyamines

Egorov

Borisova

et al. 2021

Fine Chem. Technol.

View full text Add to dashboard Cite

Objectives. Biogenic polyamines are widely present in nature. They are characteristic of both protozoan cells and multicellular organisms. These compounds have a wide range of biological functions and are necessary for normal growth and development of cells. Violation of polyamine homeostasis can cause significant abnormalities in cell functioning, provoking various pathological processes, including oncological and neuropsychiatric diseases. The impact on the “polyamine pathway” is an attractive basis for the creation of many pharmacological agents with a diverse spectrum of action. The purpose of this review is to summarize the results of the studies devoted to understanding the biological activity of compounds of the polyamine series, comparing their biological action with action on certain molecular targets. Due to the structural diversity of this group of substances, it is impossible to fully reflect the currently available data in one review. Therefore, in this work, the main attention is paid to the derivatives, acyclic saturated polyamines.Results. The following aspects are considered: biological functionality, biosynthesis and catabolism, cell transport, and localization of biogenic polyamines in the living systems. Structural analogs and derivatives of biogenic polyamines with antitumor, neuroprotective, antiarrhythmic, antiparasitic, antibacterial, and other biological activities are represented; the relationship between biological activity and the target of exposure is reflected. It was found that the nature of the substituent, the number of cationic centers, and the length of the polyamine chain have a great influence on the nature of the effect.Conclusions. At present, the use of polyamine structures is restrained by cytotoxicity and nonspecific toxic effects on the central nervous system. Further research in the field of biochemistry, cell transport, and a deeper understanding of receptor interaction mechanisms will help making polyamines as the basis for potential drug formulation.

show abstract

Polyamines and its analogue modulates amyloid fibrillation in lysozyme: A comparative investigation

Cited by 9 publications

References 100 publications

Polyamines Mediate Folding of Primordial Hyperacidic Helical Proteins

Polyamines Mediate Folding of Primordial Hyperacidic Helical Proteins

Effects of Qi-Fu-Yin on aging of APP/PS1 transgenic mice by regulating the intestinal microbiome

Structure and biological action of analogs and derivatives of biogenic polyamines

Contact Info

Product

Resources

About