Topic Editors

Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso D’Augusto 237, 47921 Rimini, Italy
Department for Life Quality Studies, University of Bologna, 40126 Bologna, Italy

Neuroprotection by Drugs, Nutraceuticals and Physical Activity, 2nd Volume

Abstract submission deadline
closed (30 November 2023)
Manuscript submission deadline
closed (31 January 2024)
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Topic Information

Dear Colleagues,

Acute and chronic neurodegenerative diseases, such as stroke, brain trauma, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease, are associated with high morbidity and mortality rates. A characteristic of these neurodegenerative diseases is selective neuronal dysfunction and death. The symptoms and the exacerbations of these diseases are, however, very different according to their specific pathways of neuronal impairment. Several mechanisms can lead to neuronal dysfunction and death, including calcium overload, excitatory amino acid release, oxidative stress, inflammation and microglial activation, protein misfolding, proteostasis and mitochondrial disfunction. The clinical management of these diseases is currently highly critical, as therapeutic strategies are often limited to relieving symptoms rather than treating the disease. Hence, the development of neuroprotective strategies to prevent or delay neuronal impairment is at the center of the current 21st-century research agenda in biomedicine. The scientific community, in addition to focusing on the development of effective new neuroprotective drugs, is also exploring non-pharmacological approaches using food components, such as nutraceuticals, and physical activity. In this regard, several studies show that nutraceuticals and physical activity have similar or complementary neuroprotection mechanisms, suggesting new integrated approaches with pharmacological interventions to enhance their neuroprotective effects. We invite you to submit your research findings to this Special Issue, which has the aim to present the updated state-of-the-art research on the potential mechanisms of neuroprotection at pre-clinical and clinical levels that are mediated by drugs, nutraceuticals and physical activity. Original research articles, review articles, clinical trials, and meta-analyses are welcome.

Dr. Cristina Angeloni
Prof. Dr. Andrea Tarozzi
Topic Editors

Keywords

  • old and new drugs
  • food supplements, nutraceuticals, and functional foods
  • physical activity and exercise
  • integrated neuroprotective interventions
  • neuroprotective mechanisms
  • neuroprotective strategies
  • new targets for neuroprotection
  • prevention of eurodegeneration
  • neurodegenerative diseases

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Biomedicines
biomedicines
4.7 3.7 2013 15.4 Days CHF 2600
Biomolecules
biomolecules
5.5 8.3 2011 16.9 Days CHF 2700
Current Issues in Molecular Biology
cimb
3.1 2.4 1999 13.5 Days CHF 2200
International Journal of Molecular Sciences
ijms
5.6 7.8 2000 16.3 Days CHF 2900
Pharmaceuticals
pharmaceuticals
4.6 4.7 2004 14.6 Days CHF 2900

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Published Papers (5 papers)

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27 pages, 9750 KiB  
Article
Chitosan Nanoparticles Loaded with Quercetin and Valproic Acid: A Novel Approach for Enhancing Antioxidant Activity against Oxidative Stress in the SH-SY5Y Human Neuroblastoma Cell Line
by Fadime Canbolat, Neslihan Demir, Ozlem Tonguc Yayıntas, Melek Pehlivan, Aslı Eldem, Tulay Kilicaslan Ayna and Mehmet Senel
Biomedicines 2024, 12(2), 287; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines12020287 - 26 Jan 2024
Cited by 1 | Viewed by 928
Abstract
Background: Multiple drug-delivery systems obtained by loading nanoparticles (NPs) with different drugs that have different physicochemical properties present a promising strategy to achieve synergistic effects between drugs or overcome undesired effects. This study aims to develop a new NP by loading quercetin (Que) [...] Read more.
Background: Multiple drug-delivery systems obtained by loading nanoparticles (NPs) with different drugs that have different physicochemical properties present a promising strategy to achieve synergistic effects between drugs or overcome undesired effects. This study aims to develop a new NP by loading quercetin (Que) and valproic acid (VPA) into chitosan. In this context, our study investigated the antioxidant activities of chitosan NPs loaded with single and dual drugs containing Que against oxidative stress. Method: The synthesis of chitosan NPs loaded with a single (Que or VPA) and dual drug (Que and VPA), the characterization of the NPs, the conducting of in vitro antioxidant activity studies, and the analysis of the cytotoxicity and antioxidant activity of the NPs in human neuroblastoma SH-SY5Y cell lines were performed. Result: The NP applications that protected cell viability to the greatest extent against H2O2-induced cell damage were, in order, 96 µg/mL of Que-loaded chitosan NP (77.30%, 48 h), 2 µg/mL of VPA-loaded chitosan NP (70.06%, 24 h), 96 µg/mL of blank chitosan NP (68.31%, 48 h), and 2 µg/mL of Que- and VPA-loaded chitosan NP (66.03%, 24 h). Conclusion: Our study establishes a successful paradigm for developing drug-loaded NPs with a uniform and homogeneous distribution of drugs into NPs. Chitosan NPs loaded with both single and dual drugs possessing antioxidant activity were successfully developed. The capability of chitosan NPs developed at the nanometer scale to sustain cell viability in SH-SY5Y cell lines implies the potential of intranasal administration of chitosan NPs for future studies, offering protective effects in central nervous system diseases. Full article
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20 pages, 3143 KiB  
Article
Identification of the Candidate mGlu2 Allosteric Modulator THRX-195518 through In Silico Method and Evaluation of Its Neuroprotective Potential against Glutamate-Induced Neurotoxicity in SH-SY5Y Cell Line
by Fadime Canbolat, Nigar Kantarci-Carsibasi, Sevim Isik, Suhair Rami Mohammed Shamshir and Münteha Girgin
Curr. Issues Mol. Biol. 2024, 46(1), 788-807; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb46010051 - 17 Jan 2024
Viewed by 785
Abstract
Glutamate (Glu) toxicity has been an important research topic in toxicology and neuroscience studies. In vitro and in vivo studies have shown that Group II metabotropic Glu2 (mGlu2) activators have cell viability effects. This study aims to determine a candidate ligand with high [...] Read more.
Glutamate (Glu) toxicity has been an important research topic in toxicology and neuroscience studies. In vitro and in vivo studies have shown that Group II metabotropic Glu2 (mGlu2) activators have cell viability effects. This study aims to determine a candidate ligand with high mGlu2 allosteric region activity among cytotoxicity-safe molecules using the in silico positioning method and to evaluate its cell viability effect in vitro. We investigated the candidate molecule’s cell viability effect on the SH-SY5Y human neuroblastoma cell line by MTT analysis. In the study, LY 379268 (agonist) and JNJ-46281222 (positive allosteric modulator; PAM) were used as control reference molecules. Drug bank screening yielded THRX-195518 (docking score being −12.4 kcal/mol) as a potential novel drug candidate that has a high docking score and has not been mentioned in the literature so far. The orthosteric agonist LY 379268 exhibited a robust protective effect in our study. Additionally, our findings demonstrate that JNJ-46281222 and THRX-195518, identified as activating the mGlu2 allosteric region through in silico methods, preserve cell viability against Glu toxicity. Therefore, our study not only emphasizes the positive effects of this compound on cell viability against Glu toxicity but also sheds light on the potential of THRX-195518, acting as a mGlu2 PAM, based on in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) data, as a candidate drug molecule. These findings underscore the potential utility of THRX-195518 against both neurotoxicity and Central Nervous System (CNS) disorders, providing valuable insights. Full article
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13 pages, 1466 KiB  
Article
The Effect of Liraglutide on Axon Regeneration and Functional Recovery after Peripheral Nerve Lesion
by Mehmet Burak Yalçın, Ejder Saylav Bora and Oytun Erbaş
Curr. Issues Mol. Biol. 2024, 46(1), 327-339; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb46010021 - 02 Jan 2024
Viewed by 1114
Abstract
Peripheral nerve injuries inflict severe consequences, necessitating innovative therapeutic strategies. This study investigates the potential of liraglutide, a glucagon-like peptide-1 receptor agonist, in mitigating the consequences of peripheral nerve injury. The existing treatment methods for such injuries underscore the importance of ongoing translational [...] Read more.
Peripheral nerve injuries inflict severe consequences, necessitating innovative therapeutic strategies. This study investigates the potential of liraglutide, a glucagon-like peptide-1 receptor agonist, in mitigating the consequences of peripheral nerve injury. The existing treatment methods for such injuries underscore the importance of ongoing translational research efforts. Thirty adult Wistar rats underwent sciatic nerve dissection and repair surgery. The nerves were surgically transected using micro scissors at a precise location located 1.5 cm proximal to the trifurcation site. The study included a control group and two experimental groups, one treated with saline (placebo group) and the other with liraglutide (experimental group) for 12 weeks. Motor function, electromyography (EMG), and biochemical and histopathological analyses were performed after 12 weeks of treatment. Electrophysiological assessments revealed that liraglutide improved the compound muscle action potential (CMAP) amplitude and motor function compared to the saline-treated group. Histological and immunohistochemical analyses demonstrated increased NGF expression, total axon number, and diameter and reduced fibrosis in the liraglutide group. Biochemical analyses illustrated liraglutide’s antioxidative properties, evidenced by reduced malondialdehyde (MDA) levels. Galectin-3 levels were suppressed and GDF-11 levels were modulated by liraglutide, indicating anti-inflammatory and anti-apoptotic effects. Liraglutide is a promising therapeutic intervention for peripheral nerve injuries, promoting functional recovery and histopathological improvement. Its multifaceted positive impact, beyond glycemic control, suggests constructive effects on the acute and chronic inflammatory processes associated with peripheral neuropathy. These findings warrant further research to elucidate molecular mechanisms and facilitate clinical translation. The study contributes valuable insights to the growing understanding of GLP-1 receptor agonists’ neuroprotective properties in the context of peripheral nerve injuries. Full article
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12 pages, 2313 KiB  
Article
Unraveling the Potential of Isorhamnetin as an Adjuvant in Depression Treatment with Escitalopram
by Omar Gammoh, Esam Y. Qnais, Rabaa Y. Athamneh, Bilal Al-Jaidi, Deniz Al-Tawalbeh, Sara Altaber, Abdelrahim Alqudah, Alaa A. A. Aljabali and Murtaza M. Tambuwala
Curr. Issues Mol. Biol. 2023, 45(9), 7668-7679; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45090484 - 21 Sep 2023
Viewed by 1401
Abstract
Oxidative stress and inflammation are implicated in depression. While selective serotonin reuptake inhibitors (SSRIs) like escitalopram are commonly prescribed as first-line treatments, their inconsistent efficacy and delayed onset of action necessitates the exploration of adjunctive therapies. Isorhamnetin, a flavonol, has shown antioxidant and [...] Read more.
Oxidative stress and inflammation are implicated in depression. While selective serotonin reuptake inhibitors (SSRIs) like escitalopram are commonly prescribed as first-line treatments, their inconsistent efficacy and delayed onset of action necessitates the exploration of adjunctive therapies. Isorhamnetin, a flavonol, has shown antioxidant and anti-inflammatory properties that makes exploring its antidepressant effect attractive. This study aims to investigate the adjuvant potential of isorhamnetin in combination with escitalopram to enhance its antidepressant efficacy in a lipopolysaccharide (LPS)-induced depression model using Swiss albino mice. Behavioral paradigms, such as the forced swim test and open field test, were employed to assess depressive symptoms, locomotion, and sedation. Additionally, enzyme-linked immunosorbent assays were utilized to measure Nrf2, BDNF, HO-1, NO, and IL-6 levels in the prefrontal cortex and hippocampus. The results demonstrate that isorhamnetin significantly improves the antidepressant response of escitalopram, as evidenced by reduced floating time in the forced swim test. Moreover, isorhamnetin enhanced antidepressant effects of escitalopram and effectively restored depleted levels of Nrf2, BDNF, and HO-1 in the cortex caused by LPS-induced depression. Isorhamnetin shows promise in enhancing the efficacy of conventional antidepressant therapy through antioxidant and anti-inflammatory effects. Full article
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17 pages, 10420 KiB  
Article
Effects of Whole-Body Vibration and Manually Assisted Locomotor Therapy on Neurotrophin-3 Expression and Microglia/Macrophage Mobilization Following Thoracic Spinal Cord Injury in Rats
by Diana Schaufler, Maria Eleni Manthou, Paschalis Theotokis, Svenja Rink-Notzon and Doychin N. Angelov
Curr. Issues Mol. Biol. 2023, 45(4), 3238-3254; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45040211 - 07 Apr 2023
Cited by 1 | Viewed by 1509
Abstract
Microglial cells play an important role in neuroinflammation and secondary damages after spinal cord injury (SCI). Progressive microglia/macrophage inflammation along the entire spinal axis follows SCI, and various factors may determine the microglial activation profile. Neurotrophin-3 (NT-3) is known to control the survival [...] Read more.
Microglial cells play an important role in neuroinflammation and secondary damages after spinal cord injury (SCI). Progressive microglia/macrophage inflammation along the entire spinal axis follows SCI, and various factors may determine the microglial activation profile. Neurotrophin-3 (NT-3) is known to control the survival of neurons, the function of synapses, and the release of neurotransmitters, while also stimulating axon plasticity and growth. We examined the effects of whole-body vibration (WBV) and forms of assisted locomotor therapy, such as passive flexion–extension (PFE) therapy, at the neuronal level after SCI, with a focus on changes in NT-3 expression and on microglia/macrophage reaction, as they play a major role in the reconstitution of CNS integrity after injury and they may critically account for the observed structural and functional benefits of physical therapy. More specifically, the WBV therapy resulted in the best overall functional recovery when initiated at day 14, while inducing a decrease in Iba1 and the highest increase in NT-3. Therefore, the WBV therapy at the 14th day appeared to be superior to the PFE therapy in terms of recovery. Functional deficits and subsequent rehabilitation depend heavily upon the inflammatory processes occurring caudally to the injury site; thus, we propose that increased expression of NT-3, especially in the dorsal horn, could potentially be the mediator of this favorable outcome. Full article
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