Polyamine Metabolism in Disease and Polyamine-Targeted Therapies
Murray-Stewart, Tracy
Polyamine Metabolism in Disease and Polyamine-Targeted Therapies - MDPI - Multidisciplinary Digital Publishing Institute 2019 - 1 electronic resource (240 p.)
Open Access
Polyamines are ubiquitous polycations essential for all cellular life. The most common polyamines in eukaryotes, spermine, spermidine, and putrescine, exist in millimolar intracellular concentrations that are tightly regulated through biosynthesis, catabolism, and transport. Polyamines interact with, and regulate, negatively charged macromolecules, including nucleic acids, proteins, and ion channels. Accordingly, alterations in polyamine metabolism affect cellular proliferation and survival through changes in gene expression and transcription, translation, autophagy, oxidative stress, and apoptosis. Dysregulation of these multifaceted polyamine functions contribute to multiple disease processes, thus their metabolism and function have been targeted for preventive or therapeutic intervention. The correlation between elevated polyamine levels and cancer is well established, and ornithine decarboxylase, the rate-limiting biosynthetic enzyme in the production of putrescine, is a bona fide transcriptional target of the Myc oncogene. Furthermore, induced polyamine catabolism contributes to carcinogenesis that is associated with certain forms of chronic infection and/or inflammation through the production of reactive oxygen species. These and other characteristics specific to cancer cells have led to the development of polyamine-based agents and inhibitors aimed at exploiting the polyamine metabolic pathway for chemotherapeutic and chemopreventive benefit. In addition to cancer, polyamines are involved in the pathologies of neurodegenerative diseases including Alzheimer’s and Parkinson’s, parasitic and infectious diseases, wound healing, ischemia/reperfusion injuries, and certain age-related conditions, as polyamines are known to decrease with age. As in cancer, polyamine-based therapies for these conditions are an area of active investigation. With recent advances in immunotherapy, interest has increased regarding polyamine-associated modulation of immune responses, as well as potential immunoregulation of polyamine metabolism, the results of which could have relevance to multiple disease processes. The goal of this Special Issue of Medical Sciences is to present the most recent advances in polyamine research as it relates to health, disease, and/or therapy.
Creative Commons
English
books978-3-03921-153-1 9783039211531 9783039211524
10.3390/books978-3-03921-153-1 doi
protein synthesis in cancer neuroblastoma epigenetics Drosophila imaginal discs pneumococcal pneumonia transgenic mice spermidine/spermine N1-acetyl transferase ?-difluoromethylornithine MYC skeletal muscle protein expression curcumin colorectal cancer autophagy human embryonic kidney 293 (HEK293) melanoma tumor immunity Snyder-Robinson Syndrome Streptococcus pneumoniae B-lymphocytes autoimmunity spermine oxidase cell differentiation diferuloylmethane immunity antizyme transgenic mouse polyamine hirsutism chemoprevention CRISPR transglutaminase polyamine analogs NF-?B spermine synthase atrophy aging oxidative stress mast cells African sleeping sickness pancreatic ductal adenocarcinoma eflornithine carcinogenesis ornithine decarboxylase polyamine transport inhibitor putrescine neutrophils spermidine untranslated region spermine polyphenol M2 macrophages polyamine transport system metabolism difluoromethylorthinine DFMO antizyme inhibitors capsule polyamine transport eosinophils MCF-7 cells difluoromethylornithine polyamine metabolism mutant BRAF polyamines cadaverine proteomics airway smooth muscle cells breast cancer X-linked intellectual disability complementation T-lymphocytes bis(ethyl)polyamine analogs antizyme 1 cancer osteosarcoma
Polyamine Metabolism in Disease and Polyamine-Targeted Therapies - MDPI - Multidisciplinary Digital Publishing Institute 2019 - 1 electronic resource (240 p.)
Open Access
Polyamines are ubiquitous polycations essential for all cellular life. The most common polyamines in eukaryotes, spermine, spermidine, and putrescine, exist in millimolar intracellular concentrations that are tightly regulated through biosynthesis, catabolism, and transport. Polyamines interact with, and regulate, negatively charged macromolecules, including nucleic acids, proteins, and ion channels. Accordingly, alterations in polyamine metabolism affect cellular proliferation and survival through changes in gene expression and transcription, translation, autophagy, oxidative stress, and apoptosis. Dysregulation of these multifaceted polyamine functions contribute to multiple disease processes, thus their metabolism and function have been targeted for preventive or therapeutic intervention. The correlation between elevated polyamine levels and cancer is well established, and ornithine decarboxylase, the rate-limiting biosynthetic enzyme in the production of putrescine, is a bona fide transcriptional target of the Myc oncogene. Furthermore, induced polyamine catabolism contributes to carcinogenesis that is associated with certain forms of chronic infection and/or inflammation through the production of reactive oxygen species. These and other characteristics specific to cancer cells have led to the development of polyamine-based agents and inhibitors aimed at exploiting the polyamine metabolic pathway for chemotherapeutic and chemopreventive benefit. In addition to cancer, polyamines are involved in the pathologies of neurodegenerative diseases including Alzheimer’s and Parkinson’s, parasitic and infectious diseases, wound healing, ischemia/reperfusion injuries, and certain age-related conditions, as polyamines are known to decrease with age. As in cancer, polyamine-based therapies for these conditions are an area of active investigation. With recent advances in immunotherapy, interest has increased regarding polyamine-associated modulation of immune responses, as well as potential immunoregulation of polyamine metabolism, the results of which could have relevance to multiple disease processes. The goal of this Special Issue of Medical Sciences is to present the most recent advances in polyamine research as it relates to health, disease, and/or therapy.
Creative Commons
English
books978-3-03921-153-1 9783039211531 9783039211524
10.3390/books978-3-03921-153-1 doi
protein synthesis in cancer neuroblastoma epigenetics Drosophila imaginal discs pneumococcal pneumonia transgenic mice spermidine/spermine N1-acetyl transferase ?-difluoromethylornithine MYC skeletal muscle protein expression curcumin colorectal cancer autophagy human embryonic kidney 293 (HEK293) melanoma tumor immunity Snyder-Robinson Syndrome Streptococcus pneumoniae B-lymphocytes autoimmunity spermine oxidase cell differentiation diferuloylmethane immunity antizyme transgenic mouse polyamine hirsutism chemoprevention CRISPR transglutaminase polyamine analogs NF-?B spermine synthase atrophy aging oxidative stress mast cells African sleeping sickness pancreatic ductal adenocarcinoma eflornithine carcinogenesis ornithine decarboxylase polyamine transport inhibitor putrescine neutrophils spermidine untranslated region spermine polyphenol M2 macrophages polyamine transport system metabolism difluoromethylorthinine DFMO antizyme inhibitors capsule polyamine transport eosinophils MCF-7 cells difluoromethylornithine polyamine metabolism mutant BRAF polyamines cadaverine proteomics airway smooth muscle cells breast cancer X-linked intellectual disability complementation T-lymphocytes bis(ethyl)polyamine analogs antizyme 1 cancer osteosarcoma