Molecular Pathology and Biomarkers of Neurodegenerative Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 10772

Special Issue Editors


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Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98122 Messina, Italy
Interests: antioxidant; anti-inflammatory
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98122 Messina, Italy
Interests: clinical biochemistry; molecular biology; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Many abiotic stresses induce the overproduction of reactive oxygen species (ROS) in humans. Being highly reactive and toxic species, they cause damage to DNA, proteins, carbohydrates and lipids, thus leading to oxidative stress. The increased production of reactive oxygen species and oxidative stress has been implicated in the pathogenesis of numerous inflammatory and neurodegenerative pathological conditions. The endogenous antioxidant response pathway protects cells from oxidative stress by increasing the expression of cytoprotective enzymes, and is regulated by the transcription factor NRF2. In addition to regulating the expression of antioxidant genes, NRF2 has also been shown to exert anti-inflammatory effects and modulate both mitochondrial function and biogenesis.

This Special Issue will focus on the role of NRF2 as a promising therapeutic target for inflammatory and neurodegenerative diseases. In particular, it will be aimed at the discovery of specific NRF2 activators that can be used as therapeutic agents. The Special Issue will feature original in vivo and in vitro reviews and studies providing evidence of the beneficial effects of antioxidant factors.

Dr. Tiziana Genovese
Dr. Daniela Impellizzeri
Dr. Rosalba Siracusa
Guest Editors

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Keywords

  • inflammatory pathologies
  • neurodegenerative diseases
  • oxidative stress
  • antioxidant enzymes
  • NRF2 activators

Published Papers (5 papers)

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Research

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16 pages, 2080 KiB  
Article
Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse Models
by Haya Hussain, Shujaat Ahmad, Syed Wadood Ali Shah, Abid Ullah, Shafiq Ur Rahman, Manzoor Ahmad, Mazen Almehmadi, Osama Abdulaziz, Mamdouh Allahyani, Ahad Amer Alsaiari, Mustafa Halawi and Edrous Alamer
Biomedicines 2022, 10(10), 2597; https://doi.org/10.3390/biomedicines10102597 - 17 Oct 2022
Cited by 7 | Viewed by 1778
Abstract
Alzheimer’s disease is the commonest form of dementia associated with short-term memory loss and impaired cognition and, worldwide, it is a growing health issue. A number of therapeutic strategies have been studied to design and develop an effective anti-Alzheimer drug. Curcumin has a [...] Read more.
Alzheimer’s disease is the commonest form of dementia associated with short-term memory loss and impaired cognition and, worldwide, it is a growing health issue. A number of therapeutic strategies have been studied to design and develop an effective anti-Alzheimer drug. Curcumin has a wide spectrum of biological properties. In this regard, the antioxidant potentials of mono-carbonyl curcumin analogues (h1h5) were investigated using in vitro antioxidant assays and hippocampal-based in vivo mouse models such as light–dark box, hole board, and Y-maze tests. In the in vitro assay, mono-carbonyl curcumin analogues h2 and h3 with methoxy and chloro-substituents, respectively, showed promising 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis-3-ethylbenzothiazo-line-6-sulfonate (ABTS) free radical scavenging activities. In the in vivo studies, scopolamine administration significantly (p < 0.001) induced oxidative stress and memory impairment in mice, in comparison to the normal control group. The pretreatment with mono-carbonyl curcumin analogues, specifically h2 and h3, significantly decreased (123.71 ± 15.23 s (p < 0.001), n = 8; 156.53 ± 14.13 s (p < 0.001), n = 8) the duration of time spent in the light chamber and significantly enhanced (253.95 ± 19.05 s (p < 0.001), n = 8, and 239.57 ± 9.98 s (p < 0.001), n = 8) the time spent in the dark compartment in the light–dark box arena. The numbers of hole pokings were significantly (p < 0.001, n = 8) enhanced in the hole board test and substantially increased the percent spontaneous alternation performance (SAP %) in the Y-maze mouse models in comparison to the stress control group. In the biomarker analysis, the significant reduction in the lipid peroxidation (MDA) level and enhanced catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) activities in the brain hippocampus reveal their antioxidant and memory enhancing potentials. However, further research is needed to find out the appropriate mechanism of reducing oxidative stress in pathological models. Full article
(This article belongs to the Special Issue Molecular Pathology and Biomarkers of Neurodegenerative Diseases)
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15 pages, 4918 KiB  
Article
Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion
by Marika Cordaro, Ramona D’Amico, Roberta Fusco, Alessio Filippo Peritore, Tiziana Genovese, Livia Interdonato, Gianluca Franco, Alessia Arangia, Enrico Gugliandolo, Rosalia Crupi, Rosalba Siracusa, Rosanna Di Paola, Salvatore Cuzzocrea and Daniela Impellizzeri
Biomedicines 2022, 10(6), 1448; https://doi.org/10.3390/biomedicines10061448 - 19 Jun 2022
Cited by 17 | Viewed by 3442
Abstract
Vascular dementia (VaD) is the second leading cause of dementia. The majority of VaD patients have cognitive abnormalities, which are caused by cerebral hypoperfusion-induced ischemia, endothelial dysfunction, oxidative stress, and neuroinflammation. Natural products are receiving increasing attention for the treatment of neuroinflammatory diseases. [...] Read more.
Vascular dementia (VaD) is the second leading cause of dementia. The majority of VaD patients have cognitive abnormalities, which are caused by cerebral hypoperfusion-induced ischemia, endothelial dysfunction, oxidative stress, and neuroinflammation. Natural products are receiving increasing attention for the treatment of neuroinflammatory diseases. The aim of this study was to investigate the molecular pathways underlying the protective effects of fisetin, a flavonoid present in many fruits and vegetables, in a mouse model of VaD induced by repeated ischemia-reperfusion (IR) of the total bilateral carotid artery. Here, we found that VaD caused brain injury, lipid peroxidation, and neuronal death in the hippocampus, as well as astrocyte and microglial activation, and reduced BDNF neurotrophic factor expression together with behavioral alterations. In addition, VaD induced the activation of inflammasome components (NLRP-3, ASC, and caspase 1), and their downstream products (IL-1β and IL-18) release and promote activation of apoptotic cell death. Fisetin attenuated histological injury, malondialdehyde levels, inflammasome pathway activation, apoptosis, as well as increased BDNF expression, reduced astrocyte, microglial activation, and cognitive deficits. In conclusion, the protective effects of fisetin could be due to the inhibition of the ROS-induced activation of NF-κB/NLRP3 inflammasome together with the activation of antioxidant Nrf2/HO-1, suggesting a possible crosstalk between these molecular pathways. Full article
(This article belongs to the Special Issue Molecular Pathology and Biomarkers of Neurodegenerative Diseases)
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0 pages, 9658 KiB  
Article
Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration
by Ramona D’Amico, Enrico Gugliandolo, Rosalba Siracusa, Marika Cordaro, Tiziana Genovese, Alessio Filippo Peritore, Rosalia Crupi, Livia Interdonato, Davide Di Paola, Salvatore Cuzzocrea, Roberta Fusco, Daniela Impellizzeri and Rosanna Di Paola
Biomedicines 2022, 10(5), 1073; https://doi.org/10.3390/biomedicines10051073 - 5 May 2022
Cited by 20 | Viewed by 2352 | Correction
Abstract
Human exposure to endocrine disruptors (EDs) has attracted considerable attention in recent years. Different studies showed that ED exposure may exacerbate the deterioration of the nervous system’s dopaminergic capacity and cerebral inflammation, suggesting a promotion of neurodegeneration. In that regard, the aim of [...] Read more.
Human exposure to endocrine disruptors (EDs) has attracted considerable attention in recent years. Different studies showed that ED exposure may exacerbate the deterioration of the nervous system’s dopaminergic capacity and cerebral inflammation, suggesting a promotion of neurodegeneration. In that regard, the aim of this research was to investigate the impact of ED exposure on the neuroinflammation and oxidative stress in an experimental model of Parkinson’s disease (PD). PD was induced by intraperitoneally injections of MPTP for a total dose of 80 mg/kg for each mouse. Mice were orally exposed to EDs, starting 24 h after the first MPTP administration and continuing through seven additional days. Our results showed that ED exposure raised the loss of TH and DAT induced by the administration of MPTP, as well as increased aggregation of α-synuclein, a key marker of PD. Additionally, oral exposure to EDs induced astrocytes and microglia activation that, in turn, exacerbates oxidative stress, perturbs the Nrf2 signaling pathway and activates the cascade of MAPKs. Finally, we performed behavioral tests to demonstrate that the alterations in the dopaminergic system also reflected behavioral and cognitive alterations. Importantly, these changes are more significant after exposure to atrazine compared to other EDs. The results from our study provide evidence that exposure to EDs may play a role in the development of PD; therefore, exposure to EDs should be limited. Full article
(This article belongs to the Special Issue Molecular Pathology and Biomarkers of Neurodegenerative Diseases)
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Review

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12 pages, 1084 KiB  
Review
Dimethyl Fumarate as Potential Treatment for Alzheimer’s Disease: Rationale and Clinical Trial Design
by Robert Sharkus, Richa Thakkar, Dennis L. Kolson and Cris S. Constantinescu
Biomedicines 2023, 11(5), 1387; https://doi.org/10.3390/biomedicines11051387 - 8 May 2023
Cited by 1 | Viewed by 1992
Abstract
Alzheimer’s Disease (AD) is a debilitating disease that leads to severe cognitive impairment and functional decline. The role of tau hyperphosphorylation and amyloid plaque deposition in the pathophysiology of AD has been well described; however, neuroinflammation and oxidative stress related to sustained microglial [...] Read more.
Alzheimer’s Disease (AD) is a debilitating disease that leads to severe cognitive impairment and functional decline. The role of tau hyperphosphorylation and amyloid plaque deposition in the pathophysiology of AD has been well described; however, neuroinflammation and oxidative stress related to sustained microglial activation is thought to play a significant role in the disease process as well. NRF-2 has been identified in modulating the effects of inflammation and oxidative stress in AD. Activation of NRF-2 leads to an increased production of antioxidant enzymes, including heme oxygenase, which has been shown to have protective effects in neurodegenerative disorders such as AD. Dimethyl fumarate and diroximel fumarate (DMF) have been approved for the use in relapsing–remitting multiple sclerosis. Research indicates that they can modulate the effects of neuroinflammation and oxidative stress through the NRF-2 pathway, and as such, could serve as a potential therapeutic option in AD. We propose a clinical trial design that could be used to assess DMF as a treatment option for AD. Full article
(This article belongs to the Special Issue Molecular Pathology and Biomarkers of Neurodegenerative Diseases)
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Other

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4 pages, 2886 KiB  
Correction
Correction: D’Amico et al. Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration. Biomedicines 2022, 10, 1073
by Ramona D’Amico, Enrico Gugliandolo, Rosalba Siracusa, Marika Cordaro, Tiziana Genovese, Alessio Filippo Peritore, Rosalia Crupi, Livia Interdonato, Davide Di Paola, Salvatore Cuzzocrea, Roberta Fusco, Daniela Impellizzeri and Rosanna Di Paola
Biomedicines 2024, 12(4), 834; https://doi.org/10.3390/biomedicines12040834 - 10 Apr 2024
Viewed by 487
Abstract
Errors in Figures [...] Full article
(This article belongs to the Special Issue Molecular Pathology and Biomarkers of Neurodegenerative Diseases)
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