Redox Balance and Proteostasis Surveillance in Neurodegenerative Disorders

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

Deadline for manuscript submissions: 28 February 2025 | Viewed by 1358

Special Issue Editors


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Guest Editor
Department of Biochemical Sciences “A. Rossi-Fanelli”, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Roma, Italy
Interests: proteostasis; oxidative stress; neurodegeneration; proteomics; Alzheimer’s disease
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E-Mail Website
Guest Editor
Department of Biochemical Sciences “A. Rossi-Fanelli”, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Roma, Italy
Interests: neurodegeneration; neuroscience; oxidative stress; autophagy; Down syndrome; Alzheimer disease; brain metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There is compelling evidence to indicate the existence of shared clinical and pathological features between different neurodegenerative disorders, the most representative being the loss of redox balance and increased oxidative stress, abnormal protein aggregation, proteasomal and/or autophagic dysfunction, inflammation, neuronal apoptosis, and mitochondrial dysfunction. Increased oxidative stress, protein aggregation, and the failure of protein degradation pathways are intimately linked factors leading to altered protein homeostasis (proteostasis). Proteostasis is essential for cell health and viability and is ensured by the coordinated regulation of protein translation, folding, trafficking, and degradation. When the equilibrium among these mechanisms is lost, aberrant proteostasis occurs, representing a central molecular hallmark of aging and neurodegeneration. Brain cells hold a broad array of responses to cope with stress conditions, including endogenous antioxidant responses, protein quality control systems, and protein degradation pathways. The above-mentioned defensive mechanisms are linked to each other and share common molecular processes; therefore, their induction, as well as their dysfunction, is frequently reciprocal.

This Special Issue, entitled “Redox Balance and Proteostasis Surveillance in Neurodegenerative Disorders”, aim to explore the latest cutting-edge and novel developments and findings in this fundamental field of research by focusing on data collected in humans and in murine models of neurodegenerative diseases. We are also eager to publish research on innovative therapeutic strategies aiming to rescue stress responses and brain proteome alterations. Suggested themes to be covered include the role of redox balance and proteostasis regulation in neurodegenerative disorders, the molecular peculiarities behind the alteration of those mechanisms, the common traits among different neurodegenerative disorders, and interventional approaches to ameliorating brain damage.

For this Special Issue, we invite authors as well as the participants of the COST Action CA20121 (https://benbedphar.org) to submit novel work or reviews establishing the importance of redox balance and proteostasis surveillance in promoting/combating age-related and neurodegenerative diseases.

I look forward to receiving your contributions.

Prof. Dr. Fabio Di Domenico
Dr. Antonella Tramutola
Guest Editors

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Keywords

  • redox homeostasis
  • oxidative stress
  • antioxidant response
  • proteostasis
  • protein folding
  • protein oxidation
  • unfolded protein response
  • ubiquitin proteosome system
  • autophagy
  • neurodegeneration

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Published Papers (1 paper)

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Review

38 pages, 1123 KiB  
Review
Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2
by Brigitta Buttari, Antonella Tramutola, Ana I. Rojo, Niki Chondrogianni, Sarmistha Saha, Alessandra Berry, Letizia Giona, Joana P. Miranda, Elisabetta Profumo, Sergio Davinelli, Andreas Daiber, Antonio Cuadrado and Fabio Di Domenico
Biomolecules 2025, 15(1), 113; https://doi.org/10.3390/biom15010113 - 13 Jan 2025
Viewed by 915
Abstract
Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular homeostasis, overseeing the expression of a wide array of genes involved in cytoprotective processes such as antioxidant and proteostasis control, mitochondrial function, inflammation, and the metabolism of lipids and glucose. [...] Read more.
Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular homeostasis, overseeing the expression of a wide array of genes involved in cytoprotective processes such as antioxidant and proteostasis control, mitochondrial function, inflammation, and the metabolism of lipids and glucose. The accumulation of misfolded proteins triggers the release, stabilization, and nuclear translocation of NRF2, which in turn enhances the expression of critical components of both the proteasomal and lysosomal degradation pathways. This process facilitates the clearance of toxic protein aggregates, thereby actively maintaining cellular proteostasis. As we age, the efficiency of the NRF2 pathway declines due to several factors including increased activity of its repressors, impaired NRF2-mediated antioxidant and cytoprotective gene expression, and potential epigenetic changes, though the precise mechanisms remain unclear. This leads to diminished antioxidant defenses, increased oxidative damage, and exacerbated metabolic dysregulation and inflammation—key contributors to age-related diseases. Given NRF2’s role in mitigating proteotoxic stress, the pharmacological modulation of NRF2 has emerged as a promising therapeutic strategy, even in aged preclinical models. By inducing NRF2, it is possible to mitigate the damaging effects of oxidative stress, metabolic dysfunction, and inflammation, thus reducing protein misfolding. The review highlights NRF2’s therapeutic implications for neurodegenerative diseases and cardiovascular conditions, emphasizing its role in improving proteostasis and redox homeostasis Additionally, it summarizes current research into NRF2 as a therapeutic target, offering hope for innovative treatments to counteract the effects of aging and associated diseases. Full article
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