Melatonin in Neuroprotection: Mechanisms, Mitochondria, and Therapeutic Potential

A Special Issue of Cells (ISSN 2073-4409) belonging to the section "Mitochondria".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 2183

Editors


E-Mail Website
Guest Editor
Section of Pharmacology and Hygiene, Department of Biomolecular Sciences, School of Pharmacy, University of Urbino Carlo Bo, Urbino, Italy
Interests: cerebral hypoxia/ischemia; neuronal death and regeneration; neuroprotection
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Section of Pharmacology and Hygiene, Department of Biomolecular Sciences, School of Pharmacy, University of Urbino Carlo Bo, Urbino, Italy
Interests: brain ischemic injury; neurodegeneration; neuroprotection; neurogenesis
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Laboratory of Basic and Translational Experimental Pharmacology, Department of Pathology, Faculty of Medical Sciences, National University of Cuyo, Mendoza, Argentina
Interests: melatonin; hypertension; renal disease; mitochondria; oxidative stress; neuroinflammation

Special Issue Information

Dear Colleagues,

Neurodegenerative disorders encompass a range of conditions marked by the progressive loss of neurons, leading to severe disability. Based on their onset and progression, they are primarily categorized as acute forms, which generally have a sudden onset (such as stroke or traumatic brain injury), or chronic forms, which progress slowly (such as Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis). Despite differences in onset and pace, these forms share common key pathological features, including mitochondrial dysfunction, oxidative stress, neuroinflammation, and protein misfolding.

Melatonin has emerged as a multifaceted neuroprotective agent whose actions extend far beyond its canonical role in circadian regulation. Increasing evidence reveals that melatonin exerts potent antioxidant, anti-inflammatory, and anti-apoptotic effects, with mitochondria representing a primary target of its protective activity. By stabilizing mitochondrial membranes, enhancing electron transport chain efficiency, and reducing reactive oxygen species generation, melatonin helps preserve cellular bioenergetics under pathological conditions. Moreover, its interaction with both membrane-bound receptors and receptor-independent pathways enables broad modulation of neuronal survival signaling. This Special Issue aims to bring together cutting-edge research and comprehensive reviews exploring the molecular mechanisms underlying melatonin’s neuroprotective actions, its role in mitochondrial integrity and quality control, and its translational potential in chronic and acute neurological disorders. Through this collection, we aim to deepen the understanding of melatonin’s biological versatility and highlight its promise as a therapeutic candidate for preserving neural function and combating neurodegeneration.

Dr. Walter Balduini
Dr. Silvia Carloni
Dr. Walter Manucha
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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly 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

  • neurodegenerative disorders
  • melatonin, neuroprotection
  • mitochondria
  • oxidative stress
  • neuroinflammation
  • mitochondrial dynamics
  • therapeutic potential

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (1 paper)

Order results
Result details
Select all
Export citation of selected articles as:

Review

28 pages, 7969 KB  
Review
Melatonin as a Pleiotropic Modulator of Mitochondrial Function and Cellular Signaling in Ischemic Brain Injury
by Georgina Ortiz-Martínez, Luis Fernando Ortega-Varela, María Esther Olvera-Cortés, Miguel Russi-Hernández, Socorro Azarell Anzures-Gutiérrez, Santos Ramírez-Medina, Laura María Rosas-Ponce and José Miguel Cervantes-Alfaro
Cells 2026, 15(12), 1084; https://doi.org/10.3390/cells15121084 - 15 Jun 2026
Viewed by 1539
Abstract
Acute ischemic stroke is one of the leading causes of mortality and disability globally, characterized by a complex and temporally structured cascade of cellular and molecular events. Although reperfusion therapies have improved outcomes, their narrow therapeutic window and limited availability leave many patients [...] Read more.
Acute ischemic stroke is one of the leading causes of mortality and disability globally, characterized by a complex and temporally structured cascade of cellular and molecular events. Although reperfusion therapies have improved outcomes, their narrow therapeutic window and limited availability leave many patients without effective treatment, highlighting the need for effective neuroprotective strategies capable of targeting multiple interconnected pathways. Melatonin has been proposed as a potential adjunctive neuroprotective agent based on its pleiotropic properties, modulating cellular signaling networks including antioxidant, anti-inflammatory, mitochondrial stabilizing, and BBB-preserving effects. Melatonin regulates key signaling pathways, thereby coordinating cellular responses to injury in multiple stages of ischemic pathophysiology, positioning it as a potential adjunctive therapy. Preclinical studies consistently demonstrate reductions in infarct volume, preservation of neuronal architecture, and improvements in neurological outcomes. However, clinical evidence remains limited to a small number of clinical trials, which suggest safety and possible early neurological benefit but are underpowered to determine long-term efficacy. Importantly, translational gaps persist regarding optimal dosing, duration of administration, and alignment with the temporal dynamics of post-ischemic injury. This review integrates current knowledge on the cellular and molecular mechanisms underlying the potential neuroprotective actions and its role as a pleiotropic modulator of ischemic injury. Full article
Show Figures

Figure 1

Back to TopTop