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Biomolecules
Special Issues
Necrotic Cell Death Mechanisms and Therapies
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Necrotic Cell Death Mechanisms and Therapies

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

Deadline for manuscript submissions: 31 December 2025 | Viewed by 3097

Special Issue Editors

Prof. Dr. Ilana Nathan

E-Mail Website
Guest Editor
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Interests: molecular mechanisms of necrosis; mitochondria; Lysosomes; reactive oxygen species (ROS); calcium signaling; caspase-independent proteases: serine proteases like CELA, as well as Cathepsin C and B, etc.; protease-based drug development against necrosis: siRNAs, small molecules; relevance to diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Boris Khalfin

E-Mail Website
Guest Editor
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Interests: necrosis; apoptosis; autophagy; proteases; protease inhibitors; elastase; chymotrypsin; cathepsins; myocardial infarction; stroke; cirrhosis

Special Issue Information

Dear Colleagues,

This Special Issue aims to delve into the intricate world of necrotic cell death, exploring its underlying mechanisms and potential therapeutic interventions.

Understanding the intricacies of necrotic cell death mechanisms is imperative for advancing our knowledge of cell biology and developing targeted therapeutic strategies. This Special Issue intends to bring together cutting-edge research and insights from experts in the field, fostering a comprehensive understanding of necrotic cell death pathways.

The importance of this Special Issue lies in its potential to unravel novel therapeutic approaches in order to mitigate pathological conditions associated with necrotic cell death. Additionally, we seek to develop innovative therapies to treat a long line of life-threatening diseases and prolong life.

In summary, this Special Issue will serve as a catalyst for advancing our understanding of necrotic cell death, which emphasizes its relevance in health and disease. The aim is to pave the way for the development of targeted therapies that hold promise for improved patient outcomes in various medical contexts and for life prolongation. In particular, the Special Issue on 'Necrotic Cell Death Mechanisms and Therapies' will explore specific molecular mechanisms and biomolecules that can be targeted to combat necrosis. 

Prof. Dr. Ilana Nathan
Dr. Boris Khalfin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • necrosis
  • mitochondria
  • lysosomes
  • reactive oxygen species (ROS)
  • calcium signalling
  • caspase-independent proteases: serine proteases like CELA, ELA, as well as cathepsin C and B etc.
  • heat shock proteins (HSPs)
  • epigenetics
  • necrosis in diseases and therapeutic intervention
  • necroptosis
  • ferroptosis
  • paraptosis
  • pyroptosis

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Published Papers (2 papers)

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Review

16 pages, 3263 KiB  
Review
Targeting Programmed Cell Death in Flap Ischemia/Reperfusion Injury
by Shengyue Liu, Xiaohe Xiong, Lei Chen, Jiaqi Hu, Ping Luo, Zhanpeng Ou and Fugui Zhang
Biomolecules 2025, 15(7), 911; https://doi.org/10.3390/biom15070911 - 20 Jun 2025
Viewed by 352
Abstract
A skin flap is a composite tissue unit comprising skin and subcutaneous fat with an intact vascular supply. Skin flaps are commonly employed for wound reconstruction, transplantation of damaged tissues, and cosmetic procedures. However, flap necrosis resulting from ischemia/reperfusion injury (IRI) is a [...] Read more.
A skin flap is a composite tissue unit comprising skin and subcutaneous fat with an intact vascular supply. Skin flaps are commonly employed for wound reconstruction, transplantation of damaged tissues, and cosmetic procedures. However, flap necrosis resulting from ischemia/reperfusion injury (IRI) is a frequent complication, leading to surgical failure. Therefore, This review systematically summarizes the mechanisms and therapeutic interventions targeting specific modalities of programmed cell death (PCD) in the context of IRI compromising flap survival. These interventions encompass a range of strategies, including preconditioning, systemic administration, and local drug delivery. Furthermore, we summarize key therapeutic targets for various types of PCD, along with shared pathways and therapies applicable across multiple PCD modalities. The findings presented in this review validate the feasibility of targeted therapies against PCD to prevent post-reconstructive flap necrosis. These findings provide novel strategies, such as targeting common pathways in PCD and leveraging diverse biomaterials, to enhance therapeutic outcomes. Further clinical investigations are warranted to target PCD pathways for the treatment of flap necrosis. Full article
(This article belongs to the Special Issue Necrotic Cell Death Mechanisms and Therapies)
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34 pages, 2009 KiB  
Review
The Multifaceted Role of Calcium Signaling in Regulated Necrosis
by Eric Perez-Rivera, Claudia Plasencia and Uris Ros
Biomolecules 2025, 15(6), 854; https://doi.org/10.3390/biom15060854 - 11 Jun 2025
Viewed by 1954
Abstract
Calcium is a versatile ion that regulates diverse intracellular processes, including cell death and survival, cytokine and chemokine production, lipid scrambling, and immune cell activation. In regulated necrosis, an early increase in cytosolic calcium is a hallmark of pathways such as pyroptosis, necroptosis, [...] Read more.
Calcium is a versatile ion that regulates diverse intracellular processes, including cell death and survival, cytokine and chemokine production, lipid scrambling, and immune cell activation. In regulated necrosis, an early increase in cytosolic calcium is a hallmark of pathways such as pyroptosis, necroptosis, and ferroptosis, and resembles the calcium surge triggered by pore-forming toxins. The complexity of calcium signaling is orchestrated by specialized channels in various cellular compartments and calcium-binding proteins that respond to localized calcium concentrations. However, the coordination of this intricate code during regulated necrosis and its connections to other calcium-driven processes remains poorly understood. This review provides an overview of the molecular mechanisms of calcium signaling in regulated necrosis, analyzing parallels with pore-forming toxin-mediated membrane damage to uncover nodes that are shared by these seemingly independent pathways. We also discuss advanced techniques for studying calcium dynamics, with high precision, that can be applied to study regulated necrosis. Calcium signaling emerges as a central hub where necrotic cell death pathways converge, shaping the unique signatures of dying cells and influencing their communication with the immune system. This integrated perspective highlights the complex and multifaceted role of calcium in cells and its implications for fundamental cellular processes. Full article
(This article belongs to the Special Issue Necrotic Cell Death Mechanisms and Therapies)
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