State-of-the-Art Neurophysiology and Biochemistry of Brain Diseases in Europe

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 9712

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Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Interests: biochemistry; oxidative stress; inflammation; ischemic injury; neurodegenerative diseases
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Special Issue Information

Dear Colleagues,

We are pleased to announce a volume dedicated to the state of the art in the biochemistry and pathophysiology of the brain.

The medical, social, and economic impact of age-related neurodegenerative diseases is immense, and is increasing rapidly as life expectancy is extended and the average age of the population shifts upward. These disorders, which include Alzheimer’s disease, Parkinson’s disease, prion diseases and amyotrophic lateral sclerosis, are due to the misfolding and aggregation of key brain proteins. Multiple sclerosis is another chronic neurological condition that is the subject of intensive research. All these disorders are related to perturbations in key cellular and molecular pathways, including those related to protein folding and degradation, neuronal plasticity, and inflammation. Recently, emerging and novel biomarkers have been identified and validated, and have had a huge impact on patients’ outcomes and improved the treatment landscape. We cordially invite experts in the field to submit original research or review articles pertaining to this important and fast-progressing field of biomedicine.

Prof. Dr. Rosanna Di Paola
Dr. Marika Cordaro
Dr. Roberta Fusco
Guest Editors

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Published Papers (4 papers)

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Research

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9 pages, 2658 KiB  
Article
Molecular Investigation of DKK3 in Cerebral Ischemic/Reperfusion Injury
by Maria Caffo, Roberta Fusco, Rosalba Siracusa, Gerardo Caruso, Valeria Barresi, Rosanna Di Paola, Salvatore Cuzzocrea, Antonino Francesco Germanò and Salvatore Massimo Cardali
Biomedicines 2023, 11(3), 815; https://doi.org/10.3390/biomedicines11030815 - 07 Mar 2023
Cited by 1 | Viewed by 1342
Abstract
Dickkopf-3 (Dkk3) is an atypical member of the Dkk family of Wnt inhibitors, which has been implicated in the pathophysiology of neurodegenerative disorders. Its role in the mechanisms of cellular degeneration and protection is still unknown. The aim of our work is to [...] Read more.
Dickkopf-3 (Dkk3) is an atypical member of the Dkk family of Wnt inhibitors, which has been implicated in the pathophysiology of neurodegenerative disorders. Its role in the mechanisms of cellular degeneration and protection is still unknown. The aim of our work is to investigate the endogenous activation of the DKK3 pathway in a model of transient occlusion of the middle cerebral artery in rats. In particular, the animals were subjected to 1 h of ischemia followed by different reperfusion times (1 h, 6 h, 12 h and 24 h) to evaluate the downstream pathway and the time course of its activation. Western blot analysis showed increased Dkk3 expression in animals with the highest time of reperfusion. The increased levels of Dkk3 were accompanied by reduced Wnt3a, Frz1 and PIWI1a expression in the cytosol while FOXM1 and β-catenin decreased in the nucleus. These molecular changes led to an increase in the apoptotic pathway, as showed by the increased expression of Caspase 3 and Bax and the reduced levels of Bcl-2, and to a decrease in neurogenesis, as shown by the decreased expression of Tbr2, Ngn2 and Pax6. In the second part of the study, we decided to employ curcumin, an activator of the Wnt/β-catenin signaling, to investigate its effect on Dkk3. In particular, curcumin was administered 1 and 6 h after ischemia, and animals were sacrificed 24 h later when the expression of Dkk3 was higher. Our data displayed that curcumin administration decreased Dkk3 expression, and increased Wnt3a, Frz1 and PIWI1a levels. Well in line with these data, curcumin administration increased nuclear β-catenin and FOXM1 expression. The down-regulation of Dkk3 by curcumin led to reduced apoptosis and increased neurogenesis. Summarizing, our results showed that Dkk3 acts as an inhibitor of Wnt/β-catenin signaling during cerebral ischemia. Additionally, its inhibition and the contextual activation of the Wnt/β-catenin pathway are protective against ischemic stroke. Full article
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12 pages, 1403 KiB  
Article
Diagnostic Cerebrospinal Fluid Biomarker in Early and Late Onset Multiple Sclerosis
by Franz Felix Konen, Malte Johannes Hannich, Philipp Schwenkenbecher, Matthias Grothe, Konrad Gag, Konstantin Fritz Jendretzky, Stefan Gingele, Kurt-Wolfram Sühs, Torsten Witte, Thomas Skripuletz and Marie Süße
Biomedicines 2022, 10(7), 1629; https://doi.org/10.3390/biomedicines10071629 - 07 Jul 2022
Cited by 4 | Viewed by 1665
Abstract
Background: The intrathecal humoral response is the characteristic diagnostic finding in the cerebrospinal fluid (CSF) analysis of patients with multiple sclerosis (MS). Although the average age of MS patients increases, little is known about the sensitivity of diagnostic markers in elderly MS patients. [...] Read more.
Background: The intrathecal humoral response is the characteristic diagnostic finding in the cerebrospinal fluid (CSF) analysis of patients with multiple sclerosis (MS). Although the average age of MS patients increases, little is known about the sensitivity of diagnostic markers in elderly MS patients. Methods: In this retrospective two-center study, intrathecal free light chains kappa fraction (FLCk IF) and oligoclonal bands (OCB) were studied in a large cohort of patients with early and late onset relapsing (RMS) and progressive (PMS) MS. Furthermore, the humoral immune profile in CSF was analyzed, including the polyspecific intrathecal immune response measured as the MRZ reaction. Results: While the frequency of CSF-specific OCB did not differ between early and late onset RMS and PMS, the sensitivity of positive FLCk IF and absolute FLCk IF values were lower in PMS. The positivity of the MRZ reaction was equally frequent in early and late onset RMS and PMS. PMS patients had higher local IgA concentrations than RMS patients (p = 0.0123). Conclusions: OCB are slightly superior to FLCk IF in progressive MS in terms of sensitivity for detecting intrathecal immunoglobulin synthesis. The MRZ reaction, as the most specific parameter for MS, is also applicable in patients with late onset and progressive MS. Full article
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Review

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30 pages, 2342 KiB  
Review
Bromodomain and Extra-Terminal Proteins in Brain Physiology and Pathology: BET-ing on Epigenetic Regulation
by Noemi Martella, Daniele Pensabene, Michela Varone, Mayra Colardo, Michele Petraroia, William Sergio, Piergiorgio La Rosa, Sandra Moreno and Marco Segatto
Biomedicines 2023, 11(3), 750; https://doi.org/10.3390/biomedicines11030750 - 01 Mar 2023
Cited by 4 | Viewed by 2732
Abstract
BET proteins function as histone code readers of acetylated lysins that determine the positive regulation in transcription of genes involved in cell cycle progression, differentiation, inflammation, and many other pathways. In recent years, thanks to the development of BET inhibitors, interest in this [...] Read more.
BET proteins function as histone code readers of acetylated lysins that determine the positive regulation in transcription of genes involved in cell cycle progression, differentiation, inflammation, and many other pathways. In recent years, thanks to the development of BET inhibitors, interest in this protein family has risen for its relevance in brain development and function. For example, experimental evidence has shown that BET modulation affects neuronal activity and the expression of genes involved in learning and memory. In addition, BET inhibition strongly suppresses molecular pathways related to neuroinflammation. These observations suggest that BET modulation may play a critical role in the onset and during the development of diverse neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s disease, fragile X syndrome, and Rett syndrome. In this review article, we summarize the most recent evidence regarding the involvement of BET proteins in brain physiology and pathology, as well as their pharmacological potential as targets for therapeutic purposes. Full article
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51 pages, 3441 KiB  
Review
Interdisciplinary Approaches to Deal with Alzheimer’s Disease—From Bench to Bedside: What Feasible Options Do Already Exist Today?
by Irene Ablinger, Katharina Dressel, Thea Rott, Anna Andrea Lauer, Michael Tiemann, João Pedro Batista, Tim Taddey, Heike Sabine Grimm and Marcus Otto Walter Grimm
Biomedicines 2022, 10(11), 2922; https://doi.org/10.3390/biomedicines10112922 - 14 Nov 2022
Cited by 1 | Viewed by 3233
Abstract
Alzheimer’s disease is one of the most common neurodegenerative diseases in the western population. The incidence of this disease increases with age. Rising life expectancy and the resulting increase in the ratio of elderly in the population are likely to exacerbate socioeconomic problems. [...] Read more.
Alzheimer’s disease is one of the most common neurodegenerative diseases in the western population. The incidence of this disease increases with age. Rising life expectancy and the resulting increase in the ratio of elderly in the population are likely to exacerbate socioeconomic problems. Alzheimer’s disease is a multifactorial disease. In addition to amyloidogenic processing leading to plaques, and tau pathology, but also other molecular causes such as oxidative stress or inflammation play a crucial role. We summarize the molecular mechanisms leading to Alzheimer’s disease and which potential interventions are known to interfere with these mechanisms, focusing on nutritional approaches and physical activity but also the beneficial effects of cognition-oriented treatments with a focus on language and communication. Interestingly, recent findings also suggest a causal link between oral conditions, such as periodontitis or edentulism, and Alzheimer’s disease, raising the question of whether dental intervention in Alzheimer’s patients can be beneficial as well. Unfortunately, all previous single-domain interventions have been shown to have limited benefit to patients. However, the latest studies indicate that combining these efforts into multidomain approaches may have increased preventive or therapeutic potential. Therefore, as another emphasis in this review, we provide an overview of current literature dealing with studies combining the above-mentioned approaches and discuss potential advantages compared to monotherapies. Considering current literature and intervention options, we also propose a multidomain interdisciplinary approach for the treatment of Alzheimer’s disease patients that synergistically links the individual approaches. In conclusion, this review highlights the need to combine different approaches in an interdisciplinary manner, to address the future challenges of Alzheimer’s disease. Full article
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