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Biomolecules
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Emerging Insights into the Role of Polyamines in Cellular Metabolism...
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Emerging Insights into the Role of Polyamines in Cellular Metabolism and Function

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 2045

Special Issue Editors

Dr. Cassandra E. Holbert

E-Mail Website
Guest Editor
Department of Biology, Loyola University Maryland, Baltimore, MD, USA
Interests: polyamine; polyamine analogue; polyamine metabolism; autophagy; ovarian cancer; ovarian; cancer; cancer biology; immune microenvironment; immune; immunotherapy; leukemia; DNA damage; epigenetics; oxidative damage; immunomodulatory
Dr. Tracy Murray Stewart

E-Mail Website
Guest Editor
The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA
Interests: rare X-linked neurodevelopmental condition Snyder–Robinson syndrome; polyamine metabolic pathway in both healthy and disease states; polyamine; HDAC10; polyaminopathy; polyamines in cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Polyamines are small, polycationic molecules essential for cell proliferation, development, and stress responses. Polyamine homeostasis is maintained through coordinated biosynthesis, catabolism, transport, and uptake from diet and microbiota. Recent studies have highlighted the roles of polyamines in metabolism and signaling across diverse species. Spermidine has gained attention for its role in autophagy, lifespan elongation, and anti-inflammatory properties. Polyamine dysregulation is common in cancer and recent work indicates that polyamines contribute to immune suppression and resistance to immunotherapy. These insights have revitalized interest in polyamine-targeting cancer therapies that address both tumor growth and immune suppression.

Beyond cancer, dysregulated polyamine metabolism is implicated in neurodegenerative diseases, wound healing, and infectious diseases. Genetic syndromes resulting from mutations in genes of the polyamine metabolic pathway offer deeper insight into the various roles of polyamines in tissues throughout the body and their roles in normal development. In plant biology, polyamines contribute to growth, stress tolerance, and defense, with potential for crop improvement under climate stress. This Special Issue of Biomolecules aims at presenting new findings in polyamine biology across model systems, emphasizing their broad relevance in health, disease, and environmental adaptation.

Dr. Cassandra E. Holbert
Dr. Tracy Murray Stewart
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • polyamine metabolism
  • putrescine
  • spermidine
  • spermine
  • polyamines in development
  • polyamines in health and disease
  • polyamines in cancer
  • polyamines in plant physiology

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Published Papers (2 papers)

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Research

23 pages, 3492 KB  
Article
Transcriptomic Analysis Reveals the Beneficial Effects of Spermidine in an ALS Mouse Model
by Cristian Fiorucci, Marianna Nicoletta Rossi, Rachele Di Santo, Illari Salvatori, Silvia Scaricamazza, Stefano Giuliani, Olga Carletta, Ermes Filomena, Davide Laurenti, Roberto Mattioli, Luciana Mosca, Cristiana Valle, Alberto Ferri, Anna Maria D'Erchia and Manuela Cervelli
Biomolecules 2026, 16(4), 566; https://doi.org/10.3390/biom16040566 - 10 Apr 2026
Viewed by 687
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of motor neurons and skeletal muscle. Gene expression analysis of the spinal cord and gastrocnemius of the SOD1-G93A ALS mouse model revealed a strong increase in inflammatory pathways and, specifically [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of motor neurons and skeletal muscle. Gene expression analysis of the spinal cord and gastrocnemius of the SOD1-G93A ALS mouse model revealed a strong increase in inflammatory pathways and, specifically in the ALS gastrocnemius, a decrease in mitochondrial transcription and an increase in ribosomal protein expression. Treatment of ALS mice with the polyamine spermidine (SPD), a promising molecule in combating neurodegeneration and muscle atrophy, is able to partially restore the expression of more than four thousand genes in gastrocnemius tissue, including the mitochondrial regulator Pgc1α, as well as all the mitochondrial encoded genes and a large class of ribosomal proteins. SPD enhanced mitochondrial bioenergetics, as evidenced by Seahorse experiments, and delayed muscle weakness in vivo, as shown by grip strength records. These findings suggest that SPD can act as a potential supplement in the therapeutic strategy for ALS, offering a foundation for further research to improve patient outcomes. Full article
(This article belongs to the Special Issue Emerging Insights into the Role of Polyamines in Cellular Metabolism and Function)
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20 pages, 3442 KB  
Article
Opposing Roles for ATP13A2 and ATP13A3 in Breast Cancer Subtype-Specific Polyamine Homeostasis
by Emily Meeus, Jan Eggermont, Sarah van Veen and Peter Vangheluwe
Biomolecules 2026, 16(2), 255; https://doi.org/10.3390/biom16020255 - 5 Feb 2026
Cited by 1 | Viewed by 778
Abstract
Polyamine homeostasis is essential for normal cellular function and is maintained through coordinated regulation of polyamine biosynthesis, catabolism, and transport. This balance is frequently disrupted in breast cancer, a biologically heterogeneous disease comprising distinct molecular subtypes. However, whether polyamine metabolism and transport are [...] Read more.
Polyamine homeostasis is essential for normal cellular function and is maintained through coordinated regulation of polyamine biosynthesis, catabolism, and transport. This balance is frequently disrupted in breast cancer, a biologically heterogeneous disease comprising distinct molecular subtypes. However, whether polyamine metabolism and transport are differentially regulated across breast cancer subtypes remains poorly defined. Here, we systematically interrogate polyamine homeostasis across representative breast cancer subtypes by integrating cell line profiling combined with analysis of publicly available patient datasets. We found subtype-associated differences across the polyamine pathway and identify polyamine transport as a key contributor to inter- and intra-subtype heterogeneity. Notably, ATP13A3 emerges as a previously unrecognized adverse prognostic marker, particularly in basal-like breast cancer, where its expression associates with proliferative and oncogenic signaling programs. In contrast, ATP13A2 shows an opposing association with patient survival, suggesting divergent functional roles for these closely related transporters. Together, our findings demonstrate that polyamine regulation in breast cancer is highly subtype dependent and highlight the importance of molecular stratification when considering polyamine-directed therapeutic strategies in breast cancer. Full article
(This article belongs to the Special Issue Emerging Insights into the Role of Polyamines in Cellular Metabolism and Function)
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