Polyamine Homeostasis in Development and Disease

Nakanishi, Shima; Cleveland, John L.

doi:10.3390/medsci9020028

Cited by 25 publications

(41 citation statements)

References 127 publications

(152 reference statements)

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“…AAs can serve as precursors to many biological compounds, including those involved nucleotide synthesis (17), redox balance (18), lipogenesis (19,20), and molecules that can fuel the TCA cycle (21). Furthermore, AAs can modulate the tumor microenvironment (22), global chromatin structures (23,24), and epigenetic factors (25)(26)(27)(28).…”

Section: Targeting Aas Dependencies In Myeloid Leukemiasmentioning

confidence: 99%

Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

et al. 2021

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Amino acid (AA) metabolism plays an important role in many cellular processes including energy production, immune function, and purine and pyrimidine synthesis. Cancer cells therefore require increased AA uptake and undergo metabolic reprogramming to satisfy the energy demand associated with their rapid proliferation. Like many other cancers, myeloid leukemias are vulnerable to specific therapeutic strategies targeting metabolic dependencies. Herein, our review provides a comprehensive overview and TCGA data analysis of biosynthetic enzymes required for non-essential AA synthesis and their dysregulation in myeloid leukemias. Furthermore, we discuss the role of the general control nonderepressible 2 (GCN2) and-mammalian target of rapamycin (mTOR) pathways of AA sensing on metabolic vulnerability and drug resistance.

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Section: Targeting Aas Dependencies In Myeloid Leukemiasmentioning

confidence: 99%

Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

et al. 2021

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“…Polyamines are ubiquitous and play critical roles in a variety of key processes, including growth, differentiation and macromolecular synthesis. Because of their relevance in rapidly proliferating cells, they have long been of interest in cancer and parasite research [ 32 , 33 , 38 , 39 , 40 , 41 , 42 ]. Furthermore, polyamines have shown protective properties, including anti-oxidant, anti-aging, and cardio- and neuroprotective functions [ 42 , 43 , 44 , 45 , 46 ].…”

Section: Significance Of Polyaminesmentioning

confidence: 99%

“…Because of their relevance in rapidly proliferating cells, they have long been of interest in cancer and parasite research [ 32 , 33 , 38 , 39 , 40 , 41 , 42 ]. Furthermore, polyamines have shown protective properties, including anti-oxidant, anti-aging, and cardio- and neuroprotective functions [ 42 , 43 , 44 , 45 , 46 ]. In contrast, their catabolic by-products have been associated with tissue damage and diseases such as cancer, heart disease, and kidney failure [ 38 , 39 , 42 , 47 , 48 , 49 ].…”

Section: Significance Of Polyaminesmentioning

confidence: 99%

Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target

Carter¹,

Kawasaki²,

Nahata³

et al. 2022

Medical Sciences

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Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity and the emergence of drug resistance. Polyamines are metabolites that play a central role in rapidly proliferating cells, and recent studies have highlighted their critical nature in Leishmania. Numerous studies using a variety of inhibitors as well as gene deletion mutants have elucidated the pathway and routes of transport, revealing unique aspects of polyamine metabolism in Leishmania parasites. These studies have also shed light on the significance of polyamines for parasite proliferation, infectivity, and host–parasite interactions. This comprehensive review article focuses on the main polyamine biosynthetic enzymes: ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine synthase, and it emphasizes recent discoveries that advance these enzymes as potential therapeutic targets against Leishmania parasites.

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“…While a PA catabolic pathway is dependent on the activity of three enzymes: N 1 -acetylpolyamine oxidase (PAOX), spermidine/spermine N 1 -acetyltransferase (SAT1), and spermine oxidase (SMOX) [7,[9][10][11]. Figure 2 The PA content in mammalian cells is tightly regulated [1][2][3] and it has been linked to important cellular roles. Polyamines are involved in the synthesis of proteins and nucleic acid and in the maintenance of their structure, in the regulation of the activity of ion channels, in cell proliferation, differentiation, and apoptosis, as well as in protection from oxidative damage [1][2][3].…”

Section: Polyamines Metabolismmentioning

confidence: 99%

“…The PA content in mammalian cells is tightly regulated [ 1 , 2 , 3 ] and it has been linked to important cellular roles. Polyamines are involved in the synthesis of proteins and nucleic acid and in the maintenance of their structure, in the regulation of the activity of ion channels, in cell proliferation, differentiation, and apoptosis, as well as in protection from oxidative damage [ 1 , 2 , 3 ]. Altered PA cellular levels have been reported in several pathological conditions of the Central Nervous System (CNS).…”

Section: Polyamines Metabolismmentioning

confidence: 99%

Transgenic Mouse Overexpressing Spermine Oxidase in Cerebrocortical Neurons: Astrocyte Dysfunction and Susceptibility to Epileptic Seizures

et al. 2022

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Polyamines are organic polycations ubiquitously present in living cells. Polyamines are involved in many cellular processes, and their content in mammalian cells is tightly controlled. Among their function, these molecules modulate the activity of several ion channels. Spermine oxidase, specifically oxidized spermine, is a neuromodulator of several types of ion channel and ionotropic glutamate receptors, and its deregulated activity has been linked to several brain pathologies, including epilepsy. The Dach-SMOX mouse line was generated using a Cre/loxP-based recombination approach to study the complex and critical functions carried out by spermine oxidase and spermine in the mammalian brain. This mouse genetic model overexpresses spermine oxidase in the neocortex and is a chronic model of excitotoxic/oxidative injury and neuron vulnerability to oxidative stress and excitotoxic, since its phenotype revealed to be more susceptible to different acute oxidative insults. In this review, the molecular mechanisms underlined the Dach-SMOX phenotype, linked to reactive astrocytosis, neuron loss, chronic oxidative and excitotoxic stress, and susceptibility to seizures have been discussed in detail. The Dach-SMOX mouse model overexpressing SMOX may help in shedding lights on the susceptibility to epileptic seizures, possibly helping to understand the mechanisms underlying epileptogenesis in vulnerable individuals and contributing to provide new molecular mechanism targets to search for novel antiepileptic drugs.

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Polyamine Homeostasis in Development and Disease

Cited by 25 publications

References 127 publications

Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target

Transgenic Mouse Overexpressing Spermine Oxidase in Cerebrocortical Neurons: Astrocyte Dysfunction and Susceptibility to Epileptic Seizures

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