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Neuroinflammation and Cellular Senescence in Brain Aging and Neurodegeneration: From Molecular Mechanisms to Therapeutic Applications

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

Deadline for manuscript submissions: 30 June 2025 | Viewed by 1825

Special Issue Editors

Dr. Jordi Olloquequi

E-Mail Website
Guest Editor
Department of Biochemistry and Physiology, Physiology Section, School of Pharmacy and Food Sciences, Universitat de Barcelona, 08028 Barcelona, Spain
Interests: pathophysiology; inflammation; cell biology; toxicology; neurodegeneration; COPD; aging and age-related disorders
Special Issues, Collections and Topics in MDPI journals
Dr. M. Emília Juan

E-Mail Website
Guest Editor
1. Departament de Bioquímica i Fisiologia, Universitat de Barcelona (UB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain
2. Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), Universitat de Barcelona (UB), Av. Prat de la Riva 171, 08921 Santa Coloma de Gramanet, Spain
Interests: nutraceuticals; functional foods; polyphenols; pentacyclic triterpenes; bioavailability; LC-MS; colon cancer; inflammation; toxicology; aging and age-related disorders

Special Issue Information

Dear Colleagues,

The complex interplay between neuroinflammation and cellular senescence represents a crucial axis in the pathogenesis of neurodegenerative disorders. This Special Issue aims to compile cutting-edge research exploring the molecular and cellular mechanisms that connect these processes to neurodegeneration, while also highlighting innovative therapeutic approaches.

We welcome contributions investigating the role of neuroinflammation-induced DNA damage, mitochondrial dysfunction, and protein aggregation in promoting cellular senescence within the central nervous system. Of particular interest are studies examining how senescent cells, through their senescence-associated secretory phenotype (SASP), modify the brain microenvironment and influence neighboring cells, including neurons, astrocytes, microglia, and oligodendrocytes.

This Special Issue will cover research on blood–brain barrier integrity, neurovascular unit dysfunction, and the influence of peripheral inflammation on central nervous system homeostasis. We encourage submissions exploring novel biomarkers for early detection of neuroinflammation and senescence, as well as innovative therapeutic strategies such as senolytic compounds, anti-inflammatory agents, cell-based therapies, and targeted drug delivery systems. Articles investigating the impact of lifestyle factors—including diet, exercise, and stress on neuroinflammation and cellular senescence—are also welcome.

The integration of various research approaches, from molecular biology and biochemistry to advanced imaging techniques, -omics technologies, and artificial intelligence-driven drug discovery platforms, will provide a comprehensive understanding of these interconnected processes. 

Dr. Jordi Olloquequi
Dr. M. Emília Juan
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. 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

  • SASP
  • glial activation
  • age-related disorders
  • neurotherapeutics
  • molecular signaling

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Published Papers (2 papers)

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Research

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12 pages, 1847 KiB  
Article
Blood Biomarkers Reflect Dementia Symptoms and Are Influenced by Cerebrovascular Lesions
by Taizen Nakase, Yasuko Tatewaki, Yumi Takano, Shuko Nomura, Hae Woon Baek and Yasuyuki Taki
Int. J. Mol. Sci. 2025, 26(5), 2325; https://doi.org/10.3390/ijms26052325 - 5 Mar 2025
Viewed by 694
Abstract
Dementia blood biomarkers are becoming increasingly important. Various factors, such as ischemic lesions and inflammation, can influence the pathomechanism of dementia. We aimed to evaluate the effects of past stroke lesions on blood biomarkers (BMs). Following approval from the institutional ethics committee, patients [...] Read more.
Dementia blood biomarkers are becoming increasingly important. Various factors, such as ischemic lesions and inflammation, can influence the pathomechanism of dementia. We aimed to evaluate the effects of past stroke lesions on blood biomarkers (BMs). Following approval from the institutional ethics committee, patients who were admitted to the memory clinic and were consented to written documents were enrolled (n = 111, average [standard deviation] age: 74.5 [9.1] years-old). Brain magnetic resonance imaging, cognitive function, and neuropsychological symptoms were analyzed. The amyloid-β 42 (Aβ42)/Aβ40 ratio, phosphorylated tau181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and Aβ42/p-tau181 ratio were assessed as plasma BMs. The patients were diagnosed with Alzheimer’s disease (n = 45), mild cognitive impairment (n = 56), depression (n = 8), and subjective cognitive impairment (n = 4). Bivariate analysis exhibited that all measured BM indicators were significantly associated with cognitive decline in patients without past stroke lesions. Whereas the patients with stroke lesions presented a significant association only between GFAP and cognitive decline (p = 0.0011). Multiple regression analysis showed that NfL significantly correlated with cognitive decline only in patients without stroke lesions (r = 0.4988, p = 0.0003) and with delusion only in those with stroke lesions (r = 0.5492, p = 0.0121). Past stroke lesions should be addressed in the assessment of the correlation between blood biomarkers and cognitive decline in dementia patients. Full article
(This article belongs to the Special Issue Neuroinflammation and Cellular Senescence in Brain Aging and Neurodegeneration: From Molecular Mechanisms to Therapeutic Applications)
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Review

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26 pages, 815 KiB  
Review
An Update of Salivary Biomarkers for the Diagnosis of Alzheimer’s Disease
by Haiying Guo, Ruihuan Yang, Weigao Cheng, Qiwen Li and Minquan Du
Int. J. Mol. Sci. 2025, 26(5), 2059; https://doi.org/10.3390/ijms26052059 - 26 Feb 2025
Viewed by 921
Abstract
Alzheimer’s disease (AD) is characterized by progressive cognition and behavior impairments. Diagnosing AD early is important for clinicians to slow down AD progression and preserve brain function. Biomarkers such as tau protein and amyloid-β peptide (Aβ) are used to aid diagnosis as clinical [...] Read more.
Alzheimer’s disease (AD) is characterized by progressive cognition and behavior impairments. Diagnosing AD early is important for clinicians to slow down AD progression and preserve brain function. Biomarkers such as tau protein and amyloid-β peptide (Aβ) are used to aid diagnosis as clinical diagnosis often lags. Additionally, biomarkers can be used to monitor AD status and evaluate AD treatment. Clinicians detect these AD biomarkers in the brain using positron emission tomography/computed tomography or in the cerebrospinal fluid using a lumbar puncture. However, these methods are expensive and invasive. In contrast, saliva collection is simple, inexpensive, non-invasive, stress-free, and repeatable. Moreover, damage to the brain parenchyma can impact the oral cavity and some pathogenic molecules could travel back and forth from the brain to the mouth. This has prompted researchers to explore biomarkers in the saliva. Therefore, this study provides an overview of the main finding of salivary biomarkers for AD diagnosis. Based on these available studies, Aβ, tau, cholinesterase enzyme activity, lactoferrin, melatonin, cortisol, proteomics, metabolomics, exosomes, and the microbiome were changed in AD patients’ saliva when compared to controls. However, well-designed studies are essential to confirm the reliability and validity of these biomarkers in diagnosing and monitoring AD. Full article
(This article belongs to the Special Issue Neuroinflammation and Cellular Senescence in Brain Aging and Neurodegeneration: From Molecular Mechanisms to Therapeutic Applications)
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