Correction to: Delineation of Neuroprotective Effects and Possible Benefits of AntioxidantsTherapy for the Treatment of Alzheimer’s Diseases by Targeting Mitochondrial-Derived Reactive Oxygen Species: Bench to Bedside

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.

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Ghrelin is neuroprotective in Parkinson’s disease: molecular mechanisms of metabolic neuroprotection

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018813479645 ◽

2013 ◽

Vol 4 (1) ◽

pp. 25-36 ◽

Cited By ~ 48

Author(s):

Jacqueline A. Bayliss ◽

Zane B. Andrews

Keyword(s):

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mitochondrial Function ◽

Therapeutic Target ◽

Molecular Mechanisms ◽

Reactive Oxygen ◽

Oxygen Species ◽

Potential Therapeutic Target ◽

Neuroprotective Effects

Ghrelin is a circulating orexigenic signal that rises with prolonged fasting and falls postprandially. Ghrelin regulates energy homeostasis by stimulating appetite and body weight; however, it also has many nonmetabolic functions including enhanced learning and memory, anxiolytic effects as well as being neuroprotective. In Parkinson’s disease, ghrelin enhances dopaminergic survival via reduced microglial and caspase activation and improved mitochondrial function. As mitochondrial dysfunction contributes to Parkinson’s disease, any agent that enhances mitochondrial function could be a potential therapeutic target. We propose that ghrelin provides neuroprotective effects via AMPK (5′ adenosine monophosphate-activated protein kinase) activation and enhanced mitophagy (removal of damaged mitochondria) to ultimately enhance mitochondrial bioenergetics. AMPK activation shifts energy balance from a negative to a neutral state and has a role in regulating mitochondrial biogenesis and reducing reactive oxygen species production. Mitophagy is important in Parkinson’s disease because damaged mitochondria produce reactive oxygen species resulting in damage to intracellular proteins, lipids and DNA predisposing them to neurodegeneration. Many genetic mutations linked to Parkinson’s disease are due to abnormal mitochondrial function and mitophagy, for example LRRK2, PINK1 and Parkin. An interaction between ghrelin and these classic Parkinson’s disease markers has not been observed, however by enhancing mitochondrial function, ghrelin or AMPK is a potential therapeutic target for slowing the progression of Parkinson’s disease symptoms, both motor and nonmotor.

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Human Wharton’s jelly mesenchymal stem cells protect neural cells from oxidative stress through paracrine mechanisms

Future Science OA ◽

10.2144/fsoa-2020-0036 ◽

2020 ◽

pp. FSO627

Author(s):

Teresa Puig-Pijuan ◽

Mariana A de Godoy ◽

Luiza Rachel Pinheiro Carvalho ◽

Victor Bodart-Santos ◽

Rafael Soares Lindoso ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Viability ◽

Reactive Oxygen ◽

Wharton’S Jelly ◽

Oxygen Species ◽

Neuroprotective Effects ◽

Wharton's Jelly ◽

Hippocampal Cultures

Aim: Mesenchymal stem cells (MSCs) have neuroprotective and immunomodulatory properties, which are partly mediated by extracellular vesicles (EVs) secretion. We aimed to evaluate the effects of human Wharton’s jelly-derived MSCs (WJ-MSCs) and their EVs on rat hippocampal cultures subjected to hydrogen peroxide (H2O2). Materials & methods: Hippocampal dissociated cultures were either co-cultured with WJ-MSCs or treated with their EVs prior to H2O2 exposure and reactive oxygen species levels and cell viability were evaluated. Results: Coculture with WJ-MSCs or pre-incubation with EVs prior to the insult reduced reactive oxygen species after H2O2 exposure. Cell viability was improved only when coculture was maintained following the insult, while EVs did not significantly improve cell viability. Conclusion: WJ-MSCs have potential antioxidant and neuroprotective effects on hippocampal cultures which might be partially mediated by EVs.

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Neuroprotective Effects of Reactive Oxygen Species Mediated by BDNF-Independent Activation of TrkB

Journal of Neuroscience ◽

10.1523/jneurosci.0755-12.2012 ◽

2012 ◽

Vol 32 (44) ◽

pp. 15521-15532 ◽

Cited By ~ 33

Author(s):

Y. Z. Huang ◽

J. O. McNamara

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Oxygen Species ◽

Neuroprotective Effects

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Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1901777116 ◽

2019 ◽

Vol 116 (22) ◽

pp. 10943-10951 ◽

Cited By ~ 70

Author(s):

Pierre Montay-Gruel ◽

Munjal M. Acharya ◽

Kristoffer Petersson ◽

Leila Alikhani ◽

Chakradhar Yakkala ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Neuronal Morphology ◽

High Dose ◽

Oxygen Species ◽

Spine Density ◽

Neuroprotective Effects ◽

Tumor Bed ◽

Conventional Dose ◽

Stress Dependent

Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy⋅s−1). Compared with conventional dose-rate (CONV; 0.07–0.1 Gy⋅s−1) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory. Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice.

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Procyanidin B2 3″-O-gallate Isolated from Reynoutria elliptica Prevents Glutamate-Induced HT22 Cell Death by Blocking the Accumulation of Intracellular Reactive Oxygen Species

Biomolecules ◽

10.3390/biom9090412 ◽

2019 ◽

Vol 9 (9) ◽

pp. 412

Author(s):

Ji Hoon Song ◽

Sil Kim ◽

Jae Sik Yu ◽

Do Hwi Park ◽

Song-Yi Kim ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Structural Diversity ◽

Neuroprotective Activity ◽

Glutamate Toxicity ◽

Oxygen Species ◽

Meoh Extract ◽

Neuroprotective Effects ◽

Ht22 Cells ◽

Extracellular Signal

In this study, we examined the neuroprotective effects of MeOH extract and bioactive compounds obtained from Reynoutria elliptica seeds using HT22 cells from the murine hippocampal cell line as its underlying molecular basis, which has not yet been elucidated. Our study showed that the MeOH extract of R. elliptica seeds strongly protected HT22 cells from glutamate toxicity. To clarify the responsible compound for the neuroprotective effects, we took an interest in procyanidins of R. elliptica since procyanidins are known to exhibit high structural diversity and neuroprotective activity. To isolate the procyanidins efficiently, a phytochemical investigation of the MeOH extract from R. elliptica seeds using the LC/MS-guided isolation approach was applied, and procyanidin B2 3″-O-gallate (1) was successfully isolated. The structure of 1 was elucidated by analyzing the nuclear magnetic resonance spectroscopic data and LC/MS analysis. The neuroprotective activities of 1 were thoroughly examined using HT22 cells. Compound 1 exhibited a strong antioxidant efficacy and blocked glutamate-mediated increase in the reactive oxygen species (ROS) accumulation. Furthermore, compound 1 significantly inhibited the phosphorylation of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase, which were increased by glutamate. These findings prove that the extract of R. elliptica seeds containing procyanidin B2 3″-O-gallate, which is a strong neuroprotective component, can be used as a functional food forattenuating and regulating neurological disorders.

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