Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
4.9
Journals
IJMS
Special Issues
The Importance of Molecular Circadian Rhythms in Health and Disease
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

The Importance of Molecular Circadian Rhythms in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 December 2025 | Viewed by 18703

Special Issue Editors

Dr. Telma Quintela

E-Mail Website
Guest Editor
CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
Interests: circadian rhythm; blood-cerebrospinal fluid barrier; drug delivery; chronotherapy
Special Issues, Collections and Topics in MDPI journals
Dr. Diana Rita Barata Costa

E-Mail Website
Guest Editor
CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
Interests: circadian rhythm; nanoformulations; drug delivery; chronotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues

A variety of an organism’s behaviors and physiological and biochemical processes occur across a span of 24 hours. A diverse range of species developed an internal time keeping system that allows the organisms to better adapt to daily variations, known as the biological clock system. On a molecular level, this clock, present in almost every tissue in mammals, is based on an autoregulatory transcription–translation feedback loop comprising clock genes/proteins. From sleep–wake cycles to hormone secretion or even foraging and activity schedules, many biological functions are associated with this scale of rhythmicity. Recently, it has been recognized that circadian rhythms play important roles in both daily physiological processes and disease mechanisms, namely cancer and neurodegenerative disorders. In fact, the dysfunction or misalignment of the circadian clock can increase the risk of disease and influence treatment responses.

Thus, this Special Issue will focus on elucidating body clocks and clock dysregulation. In addition, it intends to highlight novel findings on molecular clock manipulation in order to prevent and treat diseases.

Dr. Telma Quintela
Dr. Diana Rita Barata Costa
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 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-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • molecular clock
  • circadian dysfunction
  • health
  • chronotherapy
  • circadian rhythms

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 (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

13 pages, 2345 KB  
Article
CRY1 Lysine 151 Regulates Circadian Rhythms Through Ubiquitination-Independent Protein Interactions
by Jiawen Peng, Na Liu, Yixuan Ren, Jiahui Wang, Yanxia Jin, Xianping Wang, Weidong Wang and Jicheng Pan
Int. J. Mol. Sci. 2025, 26(16), 7962; https://doi.org/10.3390/ijms26167962 - 18 Aug 2025
Viewed by 1005
Abstract
Mammalian circadian rhythms, governing ~24 h oscillations in behavior, physiology, and hormone levels, are orchestrated by transcriptional–translational feedback loops centered around the core clock protein cryptochrome 1 (CRY1). While CRY1 ubiquitination is known to regulate clock function, the roles of specific ubiquitination sites [...] Read more.
Mammalian circadian rhythms, governing ~24 h oscillations in behavior, physiology, and hormone levels, are orchestrated by transcriptional–translational feedback loops centered around the core clock protein cryptochrome 1 (CRY1). While CRY1 ubiquitination is known to regulate clock function, the roles of specific ubiquitination sites remain unclear. Here, we identify lysine 151 (K151) as a critical residue modulating the circadian period through non-canonical mechanisms. Using site-directed mutagenesis, we generated CRY1-K151Q/R mutants mimicking constitutive deubiquitination. Circadian rescue assays in Cry1/2-deficient cells revealed period shortening (K151Q: −2.25 h; K151R: −1.4 h; n = 3, p < 0.01, Student’s t-test), demonstrating K151’s functional importance. Despite normal nuclear localization kinetics, K151Q/R mutants exhibited reduced transcriptional repression in luciferase assays, a weakened interaction with BMAL1 by the luciferase complementation assay, and enhanced binding to E3 ligase FBXL12 (but not FBXL3) while showing more stability than wild-type CRY1. Notably, the absence of ubiquitination-linked degradation or altered FBXL3 engagement suggests a ubiquitination-independent mechanism. We propose that CRY1-K151 serves as a structural hub fine-tuning circadian periodicity by modulating core clock protein interactions rather than through traditional ubiquitin-mediated turnover. These findings redefine the mechanistic landscape of post-translational clock regulation and offer new therapeutic avenues for circadian disorders. Full article
(This article belongs to the Special Issue The Importance of Molecular Circadian Rhythms in Health and Disease)
►▼ Show Figures

Figure 1

12 pages, 1668 KB  
Article
The PAS-B Domain of BMAL1 Controls Proliferation, Cellular Energetics, and Inflammatory Response in Human Monocytic Cell Line THP-1
by Yoko Gozu, Junichi Hosoi, Hiroaki Nagatomo, Kayako Ishimaru and Atsuhito Nakao
Int. J. Mol. Sci. 2025, 26(14), 6737; https://doi.org/10.3390/ijms26146737 - 14 Jul 2025
Viewed by 940
Abstract
Brain muscle ARNT-like1 (Bmal1) is a transcriptional factor, consisting of basic helix–loop–helix (bHLH) and PER-ARNT-SIM (PAS) domains, that plays a central role in circadian clock activity. However, the precise roles of the BMAL1-PAS domain, a circadian rhythm-regulating structure, remain unexplored in [...] Read more.
Brain muscle ARNT-like1 (Bmal1) is a transcriptional factor, consisting of basic helix–loop–helix (bHLH) and PER-ARNT-SIM (PAS) domains, that plays a central role in circadian clock activity. However, the precise roles of the BMAL1-PAS domain, a circadian rhythm-regulating structure, remain unexplored in monocytes. Here, we highlight the BMAL1-PAS domain as a key structure in monocyte pleiotropic functions by using human monocytic cell line THP-1. THP-1 cells lacking the BMAL1-PAS-B domain (THP-1#207) abrogated the circadian expression of core clock genes. THP-1#207 cells exhibited less proliferation, glycolysis and oxidative phosphorylation activity, and LPS-induced IL-1β production, but exhibited more production of LPS-induced IL-10 than THP-1 cells. A quantitative proteomics analysis revealed significant expression changes in ~10% metabolic enzymes in THP-1#207 cells compared to THP-1 cells, including reduction in a rate-limiting enzyme hexokinase2 (HK2) in the glycolytic pathway. Importantly, treatment of THP-1 with 2-deoxy-D-glucose (2-DG), an HK2 inhibitor, largely recapitulated the phenotypes of THP-1#207 cells. These findings suggest that the BMAL1-PAS-B domain is an important structure for the regulation of proliferation, cellular energetics, and inflammatory response in THP-1 cells, at least in part, via the control of glycolytic activity. Thus, the BMAL1-PAS-B domain may become a promising pharmacological target to control inflammation. Full article
(This article belongs to the Special Issue The Importance of Molecular Circadian Rhythms in Health and Disease)
►▼ Show Figures

Figure 1

22 pages, 1990 KB  
Article
Circadian-Tuned Peptide Drug/Gene Co-Delivery Nanocomplexes to Enhance Glioblastoma Targeting and Transfection
by Ana R. Neves, Eric Vivès, Prisca Boisguérin, Telma Quintela and Diana Costa
Int. J. Mol. Sci. 2025, 26(13), 6130; https://doi.org/10.3390/ijms26136130 - 26 Jun 2025
Viewed by 1205
Abstract
Glioblastoma is the most prevalent and aggressive form of brain malignancy. Actual treatments face several challenges due to its high aggressiveness and poor prognosis. The chemotherapeutic agent temozolomide (TMZ) has limited therapeutic efficacy, and mutations in the tumour protein p53 gene (TP53 [...] Read more.
Glioblastoma is the most prevalent and aggressive form of brain malignancy. Actual treatments face several challenges due to its high aggressiveness and poor prognosis. The chemotherapeutic agent temozolomide (TMZ) has limited therapeutic efficacy, and mutations in the tumour protein p53 gene (TP53) have been associated with treatment resistance. Thus, this study aimed to explore an innovative therapeutic strategy to enhance treatment efficacy of GBM. Previously, our team had developed a WRAP5 cell-penetrating peptide (CPP) functionalized with a transferrin receptor ligand (Tf) for the targeted delivery of TMZ and a p53-encoding plasmid to glioma cells. Our research had elucidated the circadian oscillations of the clock genes in the U87 glioma cells by employing two different computational models and observed that T16 and T8 time points revealed the highest circadian activity for Bmal1 and Per2 genes, respectively. Similar analysis was conducted for the transferrin receptor, which revealed that T7 and T8 were the key time points for its expression. A confocal microscopy study indicated the highest intracellular uptake of complexes and p53 mRNA expression at T8, the time point with the highest Per2 and transferrin receptor expression. Following mRNA analysis, the evaluation of p53 levels confirmed transcriptional changes at the protein level, and that T16 appears to be a favourable time point for enhancing therapeutic efficacy in U87 glioblastoma cells. These findings suggested that synchronizing the complexes’ administration with the biological clock of GBM cells may significantly improve glioblastoma therapeutics. Full article
(This article belongs to the Special Issue The Importance of Molecular Circadian Rhythms in Health and Disease)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

16 pages, 935 KB  
Review
The Circadian Modulators as Molecular Targets in Cancer—A Review
by Anna Wolniakowska, Joanna Roszak, Zuzanna Sobańska and Edyta Reszka
Int. J. Mol. Sci. 2025, 26(24), 11779; https://doi.org/10.3390/ijms262411779 - 5 Dec 2025
Viewed by 169
Abstract
Disruptions in the circadian clock and their link with cancer constitute a growing area of research, as evidenced by the steadily increasing number of articles on the topic. While the genes associated with circadian rhythms are relatively well characterized, the complexity of their [...] Read more.
Disruptions in the circadian clock and their link with cancer constitute a growing area of research, as evidenced by the steadily increasing number of articles on the topic. While the genes associated with circadian rhythms are relatively well characterized, the complexity of their regulation remains an important direction for study. It has been demonstrated that the interplay between genes, their expression products and external factors, such as environmental pollutants and human behavioral patterns, can lead to pathological changes, including metabolic diseases and cancer. Investigation of circadian cycle deregulations can not only provide a better understanding of carcinogenicity mechanisms and risk assessment but also create possibilities to identify new chemotherapeutics targeted at neoplastic cells. REV-ERBs and RORs are two groups of circadian clock-related nuclear factors that are examined regarding their interactions with small-molecule modulators of the circadian clock. These can act as either receptor agonists or inverse agonists, depending on the specific characteristics of a particular cancer. This review therefore summarizes and systematizes existing knowledge regarding the effectiveness of circadian modulators as chemotherapy agents, with the aim of indicating further directions for research in the field. Full article
(This article belongs to the Special Issue The Importance of Molecular Circadian Rhythms in Health and Disease)
►▼ Show Figures

Figure 1

50 pages, 1979 KB  
Review
Circadian Regulation of Neuronal Membrane Capacitance—Mechanisms and Implications for Neural Computation and Behavior
by Agnieszka Nowacka, Maciej Śniegocki, Dominika Bożiłow and Ewa Ziółkowska
Int. J. Mol. Sci. 2025, 26(21), 10766; https://doi.org/10.3390/ijms262110766 - 5 Nov 2025
Viewed by 1206
Abstract
Neuronal membrane capacitance (Cm) has traditionally been viewed as a static biophysical property determined solely by the geometric and dielectric characteristics of the lipid bilayer. Recent discoveries have fundamentally challenged this perspective, revealing that Cm exhibits robust circadian oscillations that profoundly influence neural [...] Read more.
Neuronal membrane capacitance (Cm) has traditionally been viewed as a static biophysical property determined solely by the geometric and dielectric characteristics of the lipid bilayer. Recent discoveries have fundamentally challenged this perspective, revealing that Cm exhibits robust circadian oscillations that profoundly influence neural computation and behavior. These rhythmic fluctuations in membrane capacitance are orchestrated by intrinsic cellular clocks through coordinated regulation of molecular processes including transcriptional control of membrane proteins, lipid metabolism, ion channel trafficking, and glial-mediated extracellular matrix remodeling. The dynamic modulation of Cm directly impacts the membrane time constant (τm = RmCm), thereby altering synaptic integration windows, action potential dynamics, and network synchronization across the 24 h cycle. At the computational level, circadian Cm oscillations enable neurons to shift between temporal summation and coincidence detection modes, optimizing information processing according to behavioral demands throughout the day–night cycle. These biophysical rhythms influence critical aspects of cognition including memory consolidation, attention, working memory, and sensory processing. Disruptions in normal Cm rhythmicity are increasingly implicated in neuropsychiatric and neurodegenerative disorders, including depression, schizophrenia, Alzheimer’s disease, and epilepsy, where altered membrane dynamics compromise neural circuit stability and information transfer. The integration of circadian biophysics with chronomedicine offers promising therapeutic avenues, including chronotherapeutic strategies that target membrane properties, personalized interventions based on individual chronotypes, and environmental modifications that restore healthy biophysical rhythms. This review synthesizes evidence from molecular chronobiology, cellular electrophysiology, and systems neuroscience to establish circadian Cm regulation as a fundamental mechanism linking molecular timekeeping to neural computation and behavior. Full article
(This article belongs to the Special Issue The Importance of Molecular Circadian Rhythms in Health and Disease)
►▼ Show Figures

Figure 1

22 pages, 332 KB  
Review
Circadian Disruption and Sleep Disorders in Astronauts: A Review of Multi-Disciplinary Interventions for Long-Duration Space Missions
by Hongjie Zong, Yifei Fei and Ningang Liu
Int. J. Mol. Sci. 2025, 26(11), 5179; https://doi.org/10.3390/ijms26115179 - 28 May 2025
Cited by 2 | Viewed by 3223
Abstract
As humanity advances into deep space exploration, astronauts on long-duration missions face significant challenges posed by circadian rhythm disruptions and sleep disorders, which arise from extreme environmental stressors such as microgravity, ionizing radiation, and operational workload. These disruptions not only compromise physiological and [...] Read more.
As humanity advances into deep space exploration, astronauts on long-duration missions face significant challenges posed by circadian rhythm disruptions and sleep disorders, which arise from extreme environmental stressors such as microgravity, ionizing radiation, and operational workload. These disruptions not only compromise physiological and psychological health but also impair cognitive function and mission-critical performance. In this review, we summarized established countermeasures encompassing pharmacological interventions, light-based circadian regulation, and work–rest schedule optimization alongside innovative approaches such as gut microbiota modulation and traditional Chinese medicine. Full article
(This article belongs to the Special Issue The Importance of Molecular Circadian Rhythms in Health and Disease)
31 pages, 1937 KB  
Review
Chrononutrition: Potential, Challenges, and Application in Managing Obesity
by Siti Aisyah Fuad, Rehna Paula Ginting and Min-Woo Lee
Int. J. Mol. Sci. 2025, 26(11), 5116; https://doi.org/10.3390/ijms26115116 - 26 May 2025
Cited by 5 | Viewed by 9457
Abstract
The circadian clock orchestrates nearly every aspect of physiology, aligning metabolic processes with environmental cues, such as light and food intake. While the central pacemaker in the suprachiasmatic nucleus synchronizes peripheral clocks across key metabolic tissue, feeding behavior emerges as the dominant cue [...] Read more.
The circadian clock orchestrates nearly every aspect of physiology, aligning metabolic processes with environmental cues, such as light and food intake. While the central pacemaker in the suprachiasmatic nucleus synchronizes peripheral clocks across key metabolic tissue, feeding behavior emerges as the dominant cue for peripheral clock alignment. This interaction reveals a crucial link between circadian biology and metabolism. Disruption of these processes, whether from shift work, irregular eating patterns or lifestyle misalignment, has been strongly associated with metabolic disorders, including obesity, insulin resistance and cardiometabolic diseases. Within the field of chrononutrition, strategies, such as time-restricted feeding (TRF), have gained attention for their potential to restore circadian alignment and improve metabolic health. However, translational gaps persist, as most mechanistic insights are derived from nocturnal murine models, limiting their applicability to diurnal human physiology. Moreover, human studies are confounded by interindividual variability in chronotype, behavioral patterns, and dietary compliance. This review explores the molecular underpinnings of zeitgeber signals and critically assesses the translational barriers to implementing chrononutrition across species. By integrating insights from both preclinical and clinical research, we aim to refine the potential of circadian-based dietary interventions for metabolic disease prevention and personalized nutrition. Full article
(This article belongs to the Special Issue The Importance of Molecular Circadian Rhythms in Health and Disease)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop