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Significance of Antioxidants on Aging and Neurodegeneration

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

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 17485

Special Issue Editors

Special Issue Information

Dear Colleagues,

Brain tissue is one of the most vulnerable organs to oxidative stress due to its high content of polyunsaturated fatty acids, oxygen saturation, and iron, in addition to its low antioxidant enzyme activity. Oxidative stress is involved in the pathogenesis of both aging and neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, epilepsy, depression, etc. Usually, it is uncertain if it predisposes or is a consequence of the pathological condition. The therapeutic efficacy of antioxidant treatment has been proven in preclinical and clinical studies. However, the precise mechanism underlying the effects of antioxidants is questioned, specifically as to whether is associated with direct radical scavenger action or the modulation of key signaling pathways related to neurodegeneration.

This Special Issue will involve research manuscripts, reviews, as well as short commentaries on topics related to the underlying mechanism and the role of putative signaling molecules in the effects of different natural and synthetic antioxidants against the pathophysiology of neurodegenerative diseases. It can cover reports from animal models to clinical studies in the field of aging as well as neurodegenerative diseases. Papers focused on the intrinsic role of treatments with antioxidants on oxidative stress and its impact on neurodegeneration will be considered for this Special Issue.

Prof. Dr. Jana Tchekalarova
Prof. Dr. Rumyana Tzoneva
Guest Editors

Manuscript Submission Information

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Keywords

  • antioxidants
  • brain
  • aging
  • neurodegenerative diseases
  • scavenger
  • signaling pathway

Published Papers (7 papers)

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Editorial

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3 pages, 189 KiB  
Editorial
Significance of Antioxidants on Aging and Neurodegeneration
by Jana Tchekalarova and Rumiana Tzoneva
Int. J. Mol. Sci. 2022, 23(22), 13957; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232213957 - 12 Nov 2022
Cited by 2 | Viewed by 844
Abstract
The hallmark of aging is an organism’s difficulty to maintain proper homeostasis, leading to a disrupted balance between the endogenous antioxidant system and the production of free radicals, a progressive inflammatory process, and increased susceptibility to (neurodegenerative diseases [...] Full article
(This article belongs to the Special Issue Significance of Antioxidants on Aging and Neurodegeneration)

Research

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14 pages, 2587 KiB  
Article
Impact of Melatonin Deficit on Emotional Status and Oxidative Stress-Induced Changes in Sphingomyelin and Cholesterol Level in Young Adult, Mature, and Aged Rats
by Jana Tchekalarova, Zlatina Nenchovska, Lidia Kortenska, Veselina Uzunova, Irina Georgieva and Rumiana Tzoneva
Int. J. Mol. Sci. 2022, 23(5), 2809; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052809 - 04 Mar 2022
Cited by 4 | Viewed by 1762
Abstract
The pineal gland regulates the aging process via the hormone melatonin. The present report aims to evaluate the effect of pinealectomy (pin) on behavioral and oxidative stress-induced alterations in cholesterol and sphingomyelin (SM) levels in young adult, mature and aging rats. Sham and [...] Read more.
The pineal gland regulates the aging process via the hormone melatonin. The present report aims to evaluate the effect of pinealectomy (pin) on behavioral and oxidative stress-induced alterations in cholesterol and sphingomyelin (SM) levels in young adult, mature and aging rats. Sham and pin rats aged 3, 14 and 18 months were tested in behavioral tests for motor activity, anxiety, and depression. The ELISA test explored oxidative stress parameters and SM in the hippocampus, while total cholesterol was measured in serum via a commercial autoanalyzer. Mature and aged sham rats showed low motor activity and increased anxiety compared to the youngest rats. Pinealectomy affected emotional responses, induced depressive-like behavior, and elevated cholesterol levels in the youngest rats. However, removal of the pineal gland enhanced oxidative stress by diminishing antioxidant capacity and increasing the MDA level, and decreased SM level in the hippocampus of 14-month-old rats. Our findings suggest that young adult rats are vulnerable to emotional disturbance and changes in cholesterol levels resulting from melatonin deficiency. In contrast, mature rats with pinealectomy are exposed to an oxidative stress-induced decrease in SM levels in the hippocampus. Full article
(This article belongs to the Special Issue Significance of Antioxidants on Aging and Neurodegeneration)
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15 pages, 2256 KiB  
Article
Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades
by Ahmad Jalloh, Antwoine Flowers, Charles Hudson, Dale Chaput, Jennifer Guergues, Stanley M. Stevens, Jr. and Paula C. Bickford
Int. J. Mol. Sci. 2021, 22(12), 6373; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126373 - 14 Jun 2021
Cited by 1 | Viewed by 2491
Abstract
Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of [...] Read more.
Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction. Full article
(This article belongs to the Special Issue Significance of Antioxidants on Aging and Neurodegeneration)
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13 pages, 1599 KiB  
Article
Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation
by Michaela Shishmanova-Doseva, Lyudmil Peychev, Lyubka Yoanidu, Yordanka Uzunova, Milena Atanasova, Katerina Georgieva and Jana Tchekalarova
Int. J. Mol. Sci. 2021, 22(5), 2264; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052264 - 25 Feb 2021
Cited by 14 | Viewed by 2277
Abstract
Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory [...] Read more.
Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. Methods: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. Results: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity. Full article
(This article belongs to the Special Issue Significance of Antioxidants on Aging and Neurodegeneration)
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Review

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24 pages, 559 KiB  
Review
Oxidative Stress and Aging as Risk Factors for Alzheimer’s Disease and Parkinson’s Disease: The Role of the Antioxidant Melatonin
by Jana Tchekalarova and Rumiana Tzoneva
Int. J. Mol. Sci. 2023, 24(3), 3022; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24033022 - 03 Feb 2023
Cited by 24 | Viewed by 3413
Abstract
Aging and neurodegenerative diseases share common hallmarks, including mitochondrial dysfunction and protein aggregation. Moreover, one of the major issues of the demographic crisis today is related to the progressive rise in costs for care and maintenance of the standard living condition of aged [...] Read more.
Aging and neurodegenerative diseases share common hallmarks, including mitochondrial dysfunction and protein aggregation. Moreover, one of the major issues of the demographic crisis today is related to the progressive rise in costs for care and maintenance of the standard living condition of aged patients with neurodegenerative diseases. There is a divergence in the etiology of neurodegenerative diseases. Still, a disturbed endogenous pro-oxidants/antioxidants balance is considered the crucial detrimental factor that makes the brain vulnerable to aging and progressive neurodegeneration. The present review focuses on the complex relationships between oxidative stress, autophagy, and the two of the most frequent neurodegenerative diseases associated with aging, Alzheimer’s disease (AD) and Parkinson’s disease (PD). Most of the available data support the hypothesis that a disturbed antioxidant defense system is a prerequisite for developing pathogenesis and clinical symptoms of ADs and PD. Furthermore, the release of the endogenous hormone melatonin from the pineal gland progressively diminishes with aging, and people’s susceptibility to these diseases increases with age. Elucidation of the underlying mechanisms involved in deleterious conditions predisposing to neurodegeneration in aging, including the diminished role of melatonin, is important for elaborating precise treatment strategies for the pathogenesis of AD and PD. Full article
(This article belongs to the Special Issue Significance of Antioxidants on Aging and Neurodegeneration)
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27 pages, 1405 KiB  
Review
Unusual Bioactive Compounds with Antioxidant Properties in Adjuvant Therapy Supporting Cognition Impairment in Age-Related Neurodegenerative Disorders
by Natalia Cichon, Angela Dziedzic, Leslaw Gorniak, Elzbieta Miller, Michal Bijak, Michal Starosta and Joanna Saluk-Bijak
Int. J. Mol. Sci. 2021, 22(19), 10707; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910707 - 02 Oct 2021
Cited by 8 | Viewed by 2734
Abstract
Cognitive function decline is strictly related to age, resulting in the loss of the ability to perform daily behaviors and is a fundamental clinical neurodegeneration symptom. It has been proven that an adequate diet, comprehensive nutrition, and a healthy lifestyle may significantly inhibit [...] Read more.
Cognitive function decline is strictly related to age, resulting in the loss of the ability to perform daily behaviors and is a fundamental clinical neurodegeneration symptom. It has been proven that an adequate diet, comprehensive nutrition, and a healthy lifestyle may significantly inhibit neurodegenerative processes, improving cognitive functions. Therefore, intensive research has been conducted on cognitive-enhancing treatment for many years, especially with substances of natural origin. There are several intervention programs aimed at improving cognitive functions in elderly adults. Cognitive functions depend on body weight, food consumed daily, the quality of the intestinal microflora, and the supplements used. The effectiveness in the prevention of dementia is particularly high before the onset of the first symptoms. The impact of diet and nutrition on age-associated cognitive decline is becoming a growing field as a vital factor that may be easily modified, and the effects may be observed on an ongoing basis. The paper presents a review of the latest preclinical and clinical studies on the influence of natural antioxidants on cognitive functions, with particular emphasis on neurodegenerative diseases. Nevertheless, despite the promising research results in animal models, the clinical application of natural compounds will only be possible after solving a few challenges. Full article
(This article belongs to the Special Issue Significance of Antioxidants on Aging and Neurodegeneration)
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20 pages, 1416 KiB  
Review
Elucidating the Multi-Targeted Role of Nutraceuticals: A Complementary Therapy to Starve Neurodegenerative Diseases
by Tapan Behl, Gagandeep Kaur, Aayush Sehgal, Sukhbir Singh, Saurabh Bhatia, Ahmed Al-Harrasi, Gokhan Zengin, Simona Gabriela Bungau, Mihai Alexandru Munteanu, Mihaela Cristina Brisc, Felicia Liana Andronie-Cioara and Ciprian Brisc
Int. J. Mol. Sci. 2021, 22(8), 4045; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084045 - 14 Apr 2021
Cited by 9 | Viewed by 2869
Abstract
The mechanisms underlying multifactorial diseases are always complex and challenging. Neurodegenerative disorders (NDs) are common around the globe, posing a critical healthcare issue and financial burden to the country. However, integrative evidence implies some common shared mechanisms and pathways in NDs, which include [...] Read more.
The mechanisms underlying multifactorial diseases are always complex and challenging. Neurodegenerative disorders (NDs) are common around the globe, posing a critical healthcare issue and financial burden to the country. However, integrative evidence implies some common shared mechanisms and pathways in NDs, which include mitochondrial dysfunction, neuroinflammation, oxidative stress, intracellular calcium overload, protein aggregates, oxidative stress (OS), and neuronal destruction in specific regions of the brain, owing to multifaceted pathologies. The co-existence of these multiple pathways often limits the advantages of available therapies. The nutraceutical-based approach has opened the doors to target these common multifaceted pathways in a slow and more physiological manner to starve the NDs. Peer-reviewed articles were searched via MEDLINE and PubMed published to date for in-depth research and database collection. Considered to be complementary therapy with current clinical management and common drug therapy, the intake of nutraceuticals is considered safe to target multiple mechanisms of action in NDs. The current review summarizes the popular nutraceuticals showing different effects (anti-inflammatory, antioxidant, neuro-protectant, mitochondrial homeostasis, neurogenesis promotion, and autophagy regulation) on vital molecular mechanisms involved in NDs, which can be considered as complementary therapy to first-line treatment. Moreover, owing to its natural source, lower toxicity, therapeutic interventions, biocompatibility, potential nutritional effects, and presence of various anti-oxidative and neuroprotective constituents, the nutraceuticals serve as an attractive option to tackle NDs. Full article
(This article belongs to the Special Issue Significance of Antioxidants on Aging and Neurodegeneration)
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