Polyamines are nitrogen-rich polycationic ubiquitous bioactive molecules with diverse evolutionary-conserved functions. Their activity interferes with numerous genes' expression resulting in cell proliferation and signaling modulation. The intracellular levels of polyamines are precisely controlled by evolutionary-conserved machinery. Their transient synthesis is induced by heat stress, radiation, and other traumatic stimuli in a process termed the polyamine stress response (PSR). Notably, polyamine levels decline gradually with age; and external supplementation improves lifespan in model organisms. This corresponds to cytoprotective and reactive oxygen species scavenging properties of polyamines. Paradoxically, age-associated neurodegenerative disorders are characterized by an upsurge in polyamine levels, indicating polyamine pleiotropic, adaptive, and pathogenic roles. Specifically, arginase overactivation and arginine brain deprivation have been shown to play an important role in Alzheimer’s disease (AD) pathogenesis. Here, we assert that a universal short-term PSR associated with acute stimuli is beneficial for survival. However, it becomes detrimental and maladaptive following chronic noxious stimuli, especially in an aging organism. Furthermore, we regard cellular senescence as an adaptive response to stress and suggest that PSR plays a central role in age-related neurodegenerative diseases' pathogenesis. Our perspective on AD proposes an inclusive reassessment of the causal relationships between the classical hallmarks and clinical manifestation. Consequently, we offer a novel treatment strategy predicated upon this view and suggest fine-tuning of arginase activity with natural inhibitors to preclude or halt the development of AD-related dementia.

Detection of pancreatic cancer (PC) at a resectable stage is still difficult because of the lack of accurate detection tests. The development of accurate biomarkers in low or non-invasive biofluids is essential to enable frequent tests, which would help increase the opportunity of PC detection in early stages. Polyamines have been reported as possible biomarkers in urine and saliva samples in various cancers. Here, we analyzed salivary metabolites, including polyamines, using capillary electrophoresis-mass spectrometry. Salivary samples were collected from patients with PC (n=39), chronic pancreatitis (CP, n=14) and controls (C, n=26). Polyamines, such as spermine, N1-acetylspermidine, and N1-acetylspermine, showed a significant difference between PC and C, and the combination of four metabolites including N1-acetylspermidine showed high accuracy in discriminating PC from the other two groups. These data showed the potential of saliva as a screening test for PC.

Little is known about the effect of nitrogen nutrition on seedling susceptibility to seed-borne pathogens. We have previously shown that seedlings grown under high nitrate (5 mM) conditions are less susceptible than those grown under low nitrate (0.1 mM) and ammonium (5 mM) in the Arabidopsis-Alternaria brassicicola pathosystem. However, it is not known how seedling metabolism is modulated by nitrogen nutrition, nor what is its response to pathogen infection. Here, we addressed this question using the same pathosystem and nutritive conditions, examining germination kinetics, seedling development, but also shoot ion contents, metabolome and selected gene expression. Nitrogen nutrition clearly altered the seedling metabolome. A similar metabolomic profile was observed in inoculated seedlings grown at high nitrate levels and in not inoculated-seedlings. High nitrate levels also led to specific gene expression patterns (e.g. polyamine metabolism), while other genes responded to inoculation regardless of nitrogen supply conditions. Furthermore, the metabolites best correlated with high disease symptoms were coumarate, tyrosine, hemicellulose sugars and polyamines, and those associated with low symptoms were organic acids (tricarboxylic acid pathway, glycerate, shikimate), sugars derivatives and β-alanine. Overall, our results suggest that the beneficial effect of high nitrate nutrition on seedling susceptibility is likely due to nutritive and signaling mechanisms affecting developmental plant processes detrimental to the pathogen. In particular, it may be due to a constitutively high tryptophan metabolism, as well as down regulation of oxidative stress caused by polyamine catabolism.

The infections caused by Chikungunya virus (CHIKV), genus Alphavirus, have become a health problem around the world, due to this virus’s widespread occurrence and high morbidity rate and the absence of vaccines or antiviral drugs. In this study, we analyzed a competitive inhibitor of ornithine decarboxylase—an enzyme that is key in the biosynthesis of polyamines (PAs), N-ω-chloroacetyl-L-ornithine (NCAO), which is a possible inhibitor of CHIKV replication because intracellular polyamines participate in the in vitro transcription and translation of CHIKV. NCAO does not have any cytotoxic effect on C6/36 cells even at 1000 μM at 72 h post-exposure. However, in Vero cells, a cytotoxic effect was present above 380 μM at 48 h post-exposure, which was considered when determining the inhibitory effect on viral replication. In this work, we demonstrate that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms (p <0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though mainly spermidines and spermines are present in infected cells. NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero and C6/36 cells, suggesting that this compound is a possible antiviral for CHIKV infections.

Amine containing polymers are extensively studied as special carriers for short-chain RNA (13–25 nucleotides) which are applied as gene silencing agent in gene therapy of various diseases including cancer. Elaboration of the oligonucleotide carriers requires knowledge about peculiarities of oligonucleotide - polymeric amine interaction. Critical length of the interacting chains is the important parameter which allows to design sophisticated constructions containing oligonucleotide binding segments, solubilizing, protective and aiming parts. We studied interaction of (TCAG)n, n=1-6 DNA oligonucleotides with polyethylenimine and poly(N-(3-((3-(dimethyl­amino)propyl)(methyl)amino)propyl)-N-methylacrylamide). Critical length for oligonucleotides in interaction with polymeric amines is 8-12 units and complexation at these length can be accompanied by "all-or-nothing" effects. New dimethylacrylamide based polymers with grafted polyamine chains were obtained and studied in complexation with DNA and RNA oligonucleotides. The most effective interaction and transfection activity into A549 cancer cells was found for a sample with average number of nitrogens in polyamine chain equal to 27, i.e. for a sample in which all grafted chains are longer the critical length for polymeric amine - oligonucleotide complexation.

The therapeutic effectiveness of current neurodegenerative diseases treatments is still under debate because of problems with bioavailability and a range of side effects. Fungi, which are increasingly recognized as sources of natural antioxidants and AChE enzyme inhibitors, may thus serve as potent neuroprotective agents. Previous studies have associated the anti-AChE and antioxidant activities of fungi mostly with polysaccharides and phenolic compounds, while other secondary metabolites such as polyamines (PAs) have been neglected. This study aimed to investigate eight edible and medicinal fungi from Serbia, marking the initial investigation into the neuroprotective capabilities of Postia caesia, Clitocybe odora, Clitopilus prunulus, and Morchella elata. Neuroprotective activity was examined using Ellman assay, while antioxidant capacity was tested by conducting DPPH, NO, ABTS and FRAP tests. PAs levels were determined by HPLC coupled with fluorescent detection. Ganoderma applanatum and Lepista nuda exhibited the most robust anti-AChE (98.05 ± 0.83% and 99.94 ± 3.10%, respectively) and antioxidant activities attributed to the synergistic effects of total protein, total phenolic and PAs levels. Furthermore, P. caesia displayed significant AChE inhibition (88.21 ± 4.76%), primarily linked to elevated SPD (62.98 ± 3.19%) and PUT levels (55.87 ± 3.16%). Our results highlight the need of thorough research to comprehend the intricate relationships between distinct fungus species and AChE inhibition. However, it's important to recognize that more research is required to identify the precise substances causing the reported inhibitory effects.

Plant growth-promoting rhizobacteria (PGPR) are members of the plant rhizomicrobiome that enhance plant growth and stress resistance by increasing nutrient availability to the plant, producing phytohormones or other secondary metabolites, stimulating plant defense responses against abiotic stresses and pathogens, or fixing nitrogen. The use of PGPR to increase crop yield with minimal environmental impact is a sustainable and readily applicable replacement for a portion of chemical fertilizer and pesticides required for the growth of high-yielding varieties. Increased plant health and productivity have long been gained by applying PGPR as commercial inoculants to crops, although with uneven results. The establishment of plant-PGPR relationships requires the exchange of chemical signals and nutrients between the partners, and polyamines (PAs) are an important class of compounds that act as physiological effectors and signal molecules in plant-microbe interactions. In this review we focus on the role of PAs in interactions between PGPR and plants. We describe the basic ecology of PGPR and production and function of PAs in them and in the plants with which they interact. We examine the metabolism and the roles of PAs in PGPR and plants individually and during their interaction with one another. Lastly, we describe some directions for future research.

The importance of PAs for CNS functions are well known. Less clear is, however, where PAs in the brain are derived from. Principally, there are three possibilities: (i) intake by nutrition, release into the bloodstream, and subsequent uptake from CNS capillaries, (ii) products of parenchymatous organs as the liver, and again uptake from CNS capillaries, and (iii) uptake of precursors such as arginine from the blood and subsequent local biosynthesis of polyamines within the CNS.The present investigation aimed to unequivocally answer the question, whether PAs, especially the higher ones like SPD and SPM can or cannot be taken up into the brain from the bloodstream. For this purpose a biotin-labelled analogue of SPM was synthesized, characterized, and used to visualize its uptake into brain cells subsequent to application to surviving brain slices, to the intraventricular space, or to the bloodstream.In surviving slices uptake of B-X-SPM is massive into protoplasmic and absent in fibrous type astrocytes. It is also taken up by neurons but to a lesser degree. Under in-vivo conditions astrocyte uptake of biotinylated SPM also is massive from the brain interstitial fluid subsequent to intraventricular application. In contrast, following intracardial injection there is no uptake from the bloodstream, indicating that the brain is completely dependent on the local synthesis of polyamines.

The biotic and abiotic stresses are the main causes of the loss of agricultural crops productivity, their normal growth and development in the environment. It has been calculated that two-thirds of the major crops are frequently lost due to adverse environmental conditions. The productivity of crops under unfavorable environmental stresses is apparently the main challenge to the breeders and farmers where polyamines (PAs) play diverse roles in environmental stimuli. PAs (putrescine, spermidine, and spermine) are low molecular weight positively charge compounds have the active potential power to negative charge molecules (DNA, RNA, and proteins) is widely distributed in all living organisms. Evidence showed that PAs contribute a lot of different physiological and biological functions, such as cell growth and development, controlling the cell cycle, involve in gene expression, cell signaling, replication, transcription, translation, and membrane stabilization. Naturally occurring polyamines activity acuminated to their involvement with different biotic and abiotic stresses and contribute to the survival of the plant in the environment. Here, we have described the potential mechanisms, synthesis, and various roles of PAs during stresses tolerant and disease resistance.