Naringenin Upregulates AMPK-Mediated Autophagy to Rescue Neuronal Cells From β-Amyloid (1–42) Evoked Neurotoxicity

Ahsan, Aitizaz Ul; Sharma, Vishal; Wani, Abubakar; Chopra, Mani

doi:10.1007/s12035-020-01969-4

Cited by 41 publications

(19 citation statements)

References 53 publications

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“…It has been reported that degradation and clearance of Aβ in rodent models and AD patients, are mediated through moderate autophagy upregulation by modulating AMP‐activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathways (Ntsapi, Lumkwana, Swart, du Toit, & Loos, 2018). It was demonstrated that treatment of Neuro2a (N2a) cells and primary mouse neurons with NRG‐induced AMPK activation, which inhibited mammalian target of rapamycin (mTOR) or directly induced phosphorylating unc‐51‐like kinase 1 (ULK1) as an activator of autophagy, leading to suppression of Aβ accumulation (Ahsan, Sharma, Wani, & Chopra, 2020). It was also found that Aβ by inducing apoptosis, oxidative stress, tau hyper‐phosphorylation, and senile plaques formation, causes neural damage; however, NRG provided neuroprotective effects through its antioxidant and antiinflammatory properties against Aβ neurotoxicity (Md et al, 2018).…”

Section: Nrg Against Natural Toxinsmentioning

confidence: 99%

A review on the protective effects of naringenin against natural and chemical toxic agents

Naraki

Rezaee

Karimi

2021

Phytotherapy Research

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Naringenin (NRG), as a flavanone from flavonoids family, is widely found in grapefruit, lemon tomato, and Citrus fruits. NRG has shown strong anti‐inflammatory and antioxidant activities in body organs via mechanisms such as enhancement of glutathione S‐transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and catalase (CAT) activity, but reduction of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and malondialdehyde (MDA). Furthermore, NRG anti‐apoptotic potential was indicated to be mediated by regulating B‐cell lymphoma (Bcl‐2), Bcl‐2‐associated X protein (Bax) and caspase3/9. Overall, these properties make NRG a highly fascinating compound with beneficial pharmacological effects. Based on the literature, NRG‐induced protective effects against toxicities produced by natural toxins, pharmaceuticals, heavy metals, and environmental chemicals, were mainly mediated via suppression of lipid peroxidation, oxidative stress (through boosting the antioxidant arsenal), and inflammatory factors (e.g., TNF‐α, interleukin [IL]‐6, IL‐10, and IL‐12), and activation of PI3K/Akt and MAPK survival signaling pathways. Despite considerable body of evidence on protective properties of NRG against a variety of toxic compounds, more well‐designed experimental studies and particularly, clinical trials are required before reaching a concrete conclusion. The present review discusses how NRG protects against the above‐noted toxic compounds.

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Section: Nrg Against Natural Toxinsmentioning

confidence: 99%

A review on the protective effects of naringenin against natural and chemical toxic agents

Naraki

Rezaee

Karimi

2021

Phytotherapy Research

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“…AD is characterized by Aβ aggregates, which generate FR-induced oxidative stress and inhibit autophagic degradation. Autophagy inhibition in the presence of Aβ peptides is carried out through AMPK signaling inhibition (Ahsan et al 2020). Different natural biomolecules with antioxidant properties have been implemented in the regulation of autophagic degradation through FRs.…”

Section: Apoptosis and Autophagymentioning

confidence: 99%

Free radical biology in neurological manifestations: mechanisms to therapeutics interventions

Tripathi

Gupta

Sahu

et al. 2021

Environ Sci Pollut Res

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Recent advancements and growing attention about free radicals (ROS) and redox signaling enable the scientific fraternity to consider their involvement in the pathophysiology of inflammatory diseases, metabolic disorders, and neurological defects. Free radicals increase the concentration of reactive oxygen and nitrogen species in the biological system through different endogenous sources and thus increased the overall oxidative stress. An increase in oxidative stress causes cell death through different signaling mechanisms such as mitochondrial impairment, cell-cycle arrest, DNA damage response, inflammation, negative regulation of protein, and lipid peroxidation. Thus, an appropriate balance between free radicals and antioxidants becomes crucial to maintain physiological function. Since the 1brain requires high oxygen for its functioning, it is highly vulnerable to free radical generation and enhanced ROS in the brain adversely affects axonal regeneration and synaptic plasticity, which results in neuronal cell death. In addition, increased ROS in the brain alters various signaling pathways such as apoptosis, autophagy, inflammation and microglial activation, DNA damage response, and cell-cycle arrest, leading to memory and learning defects. Mounting evidence suggests the potential involvement of micro-RNAs, circular-RNAs, natural and dietary compounds, synthetic inhibitors, and heat-shock proteins as therapeutic agents to combat neurological diseases. Herein, we explain the mechanism of free radical generation and its role in mitochondrial, protein, and lipid peroxidation biology. Further, we discuss the negative role of free radicals in synaptic plasticity and axonal regeneration through the modulation of various signaling molecules and also in the involvement of free radicals in various neurological diseases and their potential therapeutic approaches.

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“…Luteolin-7-O-glucoside was found to protect neurons through activation of the estrogen-receptor-mediated signaling pathway in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced mice [ 248 ]. Naringenin was shown to target mitochondrial membrane potential, and higher ATP levels and paraquat-induced mRNA expressions of dopamine receptor, dopamine transporter, leucine-rich repeat kinase 2, alpha-synuclein, β-catenin, caspase-3, and BDNF genes [ 249 ], and upregulated AMPK-mediated autophagy to prevent neuronal cells from β-Amyloid (1–42) evoked neurotoxicity [ 250 ].…”

Section: Phytoconstituents’ Other Modes Of Action In Nddsmentioning

confidence: 99%

Role of Phytoconstituents as PPAR Agonists: Implications for Neurodegenerative Disorders

2021

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Peroxisome proliferator-activated receptors (PPAR-γ, PPAR-α, and PPAR-β/δ) are ligand-dependent nuclear receptors that play a critical role in the regulation of hundreds of genes through their activation. Their expression and targeted activation play an important role in the treatment of a variety of diseases, including neurodegenerative, cardiovascular, diabetes, and cancer. In recent years, several reviews have been published describing the therapeutic potential of PPAR agonists (natural or synthetic) in the disorders listed above; however, no comprehensive report defining the role of naturally derived phytoconstituents as PPAR agonists targeting neurodegenerative diseases has been published. This review will focus on the role of phytoconstituents as PPAR agonists and the relevant preclinical studies and mechanistic insights into their neuroprotective effects. Exemplary research includes flavonoids, fatty acids, cannabinoids, curcumin, genistein, capsaicin, and piperine, all of which have been shown to be PPAR agonists either directly or indirectly. Additionally, a few studies have demonstrated the use of clinical samples in in vitro investigations. The role of the fruit fly Drosophila melanogaster as a potential model for studying neurodegenerative diseases has also been highlighted.

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Naringenin Upregulates AMPK-Mediated Autophagy to Rescue Neuronal Cells From β-Amyloid (1–42) Evoked Neurotoxicity

Cited by 41 publications

References 53 publications

A review on the protective effects of naringenin against natural and chemical toxic agents

A review on the protective effects of naringenin against natural and chemical toxic agents

Free radical biology in neurological manifestations: mechanisms to therapeutics interventions

Role of Phytoconstituents as PPAR Agonists: Implications for Neurodegenerative Disorders

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