Special Issue "Polyamine Metabolism in Health and Disease: Potential for Polyamine-Targeted Therapies and Prevention"
Deadline for manuscript submissions: 31 July 2021.
Interests: polyamine metabolism; antizyme; ornithine decarboxylase; ubiquitin-independent protein degradation; proteasome; cancer biology; cancer metabolism
Polyamines are highly charged bioactive substances presented ubiquitously in species from bacteria to humans. Mammalian cells have three major polyamines—putrescine, spermidine, and spermine—at concentrations that range from micromolar to millimolar. Cellular polyamine concentration is highly regulated by polyamine-dependent negative feedback regulation of ornithine decarboxylase (ODC), a rate-limiting enzyme for polyamine biosynthesis. Polyamines are also taken up and exported through putative cellular membrane transporters. The functions of cellular polyamines are highly diversified, and they are involved in cell growth; cell division; apoptosis; autophagy; oxidative stress; ion channel activity; various diseases such as cancer, Alzheimer’s, and Parkinson’s diseases; stroke; and infectious diseases caused by viruses, bacteria, fungi, and parasites. In addition, recent reports suggest that spermidine exerts cardioprotective effects and that its supplementation extends the lifespan of mice through autophagy signaling. In cancer cells, polyamine concentrations are elevated in response to excessive growth signals resulting from amplification and/or abnormalities of oncogenes and/or tumor suppressor genes. Considering these tumor characteristics, difluoromethyl ornithine (DFMO), which is a suicide inhibitor of ODC, was used in clinical trials to suppress tumor growth; however, it had no effect on tumor growth alone. Nevertheless, used in combination with polyamine transport inhibitor, it is likely to be effective for reducing tumor progression. As represented by the Warburg effect, cancer cells have a distinctive metabolic flow compared with normal cells. Accordingly, detailed analysis on polyamine and polyamine-related metabolism, including energy metabolism, will be needed to clarify cancer cell biology and to search therapeutic targets and biomarkers. Recent comprehensive analysis of brain metabolites in patients for Parkinson’s disease suggest that N1, N8-diacetylspermidine levels have the potential to be diagnostic biomarkers of this disease. The aim of this Special Issue of Medical Sciences is to present the latest polyamine research in health and disease and to explore the potential for polyamine-targeted medical applications.
Dr. Noriyuki Murai
Manuscript Submission Information
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- Polyamine metabolism
- Polyamines in cancer
- Polyamines in health
- Polyamines in disease
- Polyamines in cancer therapy and prevention
- Polyamines as a biomarker