Oxidative Stress in Cognitive and Epigenetic Aging: A Retrospective Glance

Kandlur, Aditi; Satyamoorthy, Kapaettu; Gangadharan, Gireesh

doi:10.3389/fnmol.2020.00041

Cited by 114 publications

(77 citation statements)

References 144 publications

(151 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Factors contributing to OS in the brain include excitotoxicity, depletion of the cellular antioxidant system, high susceptibility to lipid peroxidation, and high oxygen demand [ 41 ]. OS may lead to mitochondrial dysfunction, which further results in the excessive ROS generation and establishes a vicious cycle of OS [ 42 , 43 ]. Moreover, the endoplasmic reticulum (ER), a site for protein folding, also takes part in ROS generation [ 44 ].…”

Section: Pathophysiology Of Brain Disordersmentioning

confidence: 99%

Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

et al. 2020

View full text Add to dashboard Cite

Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP+) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer’s disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development.

show abstract

Section: Pathophysiology Of Brain Disordersmentioning

confidence: 99%

Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Network pharmacology reveals the complex antiaging mechanism of resveratrol through multitarget, multi-pathway and multi-pathway, and discusses the potential antiaging target of resveratrol, which provides clues and reference directions for the follow-up animal experiments, and lays a good foundation for further discussion of the antiaging pharmacological target and molecular mechanism of resveratrol. Aging is closely related to oxidative stress, endoplasmic reticulum stress and apoptosis (Chen G. et al, 2020;Kandlur et al, 2020). SOD, GSH-Px, CAT, AE, MDA are considered to be related to oxidative stress, and they were found that SOD, GSH-Px, CAT, AE, MDA worked as important parameters reflecting the potential antiaging ability of the body by many previous reasearches (Akbulut et al, 2009;Hui et al, 2020;Song et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Aging is closely related to oxidative stress, endoplasmic reticulum stress and apoptosis ( Chen G. et al., 2020 ; Kandlur et al., 2020 ). SOD, GSH-Px, CAT, AE, MDA are considered to be related to oxidative stress, and they were found that SOD, GSH-Px, CAT, AE, MDA worked as important parameters reflecting the potential antiaging ability of the body by many previous reasearches ( Akbulut et al., 2009 ; Hui et al., 2020 ; Wang L. et al., 2020 ; Song et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Verification of Resveratrol Inhibits Intestinal Aging by Downregulating ATF4/Chop/Bcl-2/Bax Signaling Pathway: Based on Network Pharmacology and Animal Experiment

Liu

Tao

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Resveratrol is one of the most well-known drugs used in the treatment of aging. However, the potential mechanisms of resveratrol on intestinal aging have not yet been fully investigated. Herein, we aimed to further explore the pharmacological mechanisms of resveratrol as a therapy for intestinal aging. We performed network construction and enrichment analysis via network pharmacology. Then a further animal experimental validation containing 20 female C57BL/6J (wild type, WT) and 16 female ATF4 +/-(knock down, KD) naturally aging mice and oral supplementary resveratrol (44 mg/kg/ day) for 30 days were conducted. The expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), linear alkylethoxylate (AE), and malondialdehyde (MDA) were measured by ELISA, the observation of pathological changes and apoptosis in intestinal tissue were performed by HE, PAS, and TUNEL staining, the ATF4/Chop/Bcl-2/Bax signaling pathway-related proteins and mRNAs expression were measured by western blotting and real-time PCR. The network pharmacology showed 132 targets of resveratrol on aging. The enrichment analysis showed resveratrol antiaging involved mainly included protein heterodimerization activity, apoptosis, etc. Then ATF4/Chop/Bcl-2/Bax signaling pathway in biological process of apoptosis was selected to verify the potential mechanisms. Animal studies showed resveratrol upregulated the relative expression of SOD, GSH-Px, CAT, AE, whereas it downregulated the relative expression of MDA in intestine compared with the control group. There was also higher relative expression of SOD, GSH-Px, CAT, AE, and lower relative expression of MDA in KD mice than that in WT mice. Moreover, there was higher relative expression of SOD, GSH-Px, CAT, AE, and lower relative expression of MDA in KD mice than that in WT mice after resveratrol treatment. Decreased ATF4, Chop, Bax but increased Bcl-2 proteins and mRNAs expression were determined after resveratrol treatment compared with the control group; lower ATF4, Chop, Bax but higher Bcl-2 proteins and mRNAs expression were found in KD mice than that in WT mice. Additionally,

show abstract

“…5 , 6 ). Numerous studies have highlighted that associations between oxidative stress and brain damage and impaired neuronal plasticity leads to aging-dependent cognitive decline [ 23 , 33 ]. In addition, IL-6 mediates the activation of neuronal NADPH oxidase and cognitive impairment in old mice [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline

et al. 2020

View full text Add to dashboard Cite

α2-Antiplasmin (α2AP), a principal physiological plasmin inhibitor, is mainly produced by the liver and kidneys, but it is also expressed in several parts of the brain, including the hippocampus and cerebral cortex. Our previous study demonstrated that α2AP knockout mice exhibit spatial memory impairment in comparison to wild-type mice, suggesting that α2AP is necessary for the fetal and/or neonatal development of the neural network for spatial memory. However, it is still unclear whether α2AP plays a role in the memory process. The present study demonstrated that adult hippocampal neurogenesis and remote spatial memory were enhanced by the injection of an anti-α2AP neutralizing antibody in WT mice, while the injection of α2AP reduced hippocampal neurogenesis and impaired remote spatial memory, suggesting that α2AP is a negative regulator in memory processing. The present study also found that the levels of α2AP in the brains of old mice were higher than those in young mice, and a negative correlation between the α2AP level and spatial working memory. In addition, aging-dependent brain oxidative stress and hippocampal inflammation were attenuated by α2AP deficiency. Thus, an age-related increase in α2AP might cause cognitive decline accompanied by brain oxidative stress and neuroinflammation. Taken together, our findings suggest that α2AP is a key regulator of the spatial memory process, and that it may represent a promising target to effectively regulate healthy brain aging.

show abstract

Oxidative Stress in Cognitive and Epigenetic Aging: A Retrospective Glance

Cited by 114 publications

References 144 publications

Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

Verification of Resveratrol Inhibits Intestinal Aging by Downregulating ATF4/Chop/Bcl-2/Bax Signaling Pathway: Based on Network Pharmacology and Animal Experiment

α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline

Contact Info

Product

Resources

About