Everolimus, a mammalian target of rapamycin inhibitor, ameliorated streptozotocin-induced learning and memory deficits via neurochemical alterations in male rats

Fanoudi, Sahar; Hosseini, Mahmoud; Alavi, Mohaddeseh Sadat; Boroushaki, Mohammad Taher; Hosseini, Azar; Sadeghnia, Hamid Reza

doi:10.17179/excli2018-1626

Cited by 10 publications

(4 citation statements)

References 91 publications

(99 reference statements)

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“…Interestingly, the interaction between everolimus-induced signature and aging-associated signature in brain hippocampus demonstrated aging-protective effect (S = 0.650, CR = 0.424, p < 10 −5 ). In vivo studies from multiple research groups showed that infusion of everolimus restored cognitive function in Alzheimer’s disease models ( Fanoudi et al, 2018 ; Cassano et al, 2019 ). As a cancer drug that is able to penetrate the blood-brain barrier ( Subbiah et al, 2015 ), everolimus’s potential mechanism in cognitive protection is the protection of intact blood-brain barrier and limited entry of proinflammatory and neurotoxic factors into the brain tissue ( Van Skike et al, 2018 ; Van Skike and Galvan, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

A Computational Framework to Characterize the Cancer Drug Induced Effect on Aging Using Transcriptomic Data

et al. 2022

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Cancer treatments such as chemotherapies may change or accelerate aging trajectories in cancer patients. Emerging evidence has shown that “omics” data can be used to study molecular changes of the aging process. Here, we integrated the drug-induced and normal aging transcriptomic data to computationally characterize the potential cancer drug-induced aging process in patients. Our analyses demonstrated that the aging-associated gene expression in the GTEx dataset can recapitulate the well-established aging hallmarks. We next characterized the drug-induced transcriptomic changes of 28 FDA approved cancer drugs in brain, kidney, muscle, and adipose tissues. Further drug-aging interaction analysis identified 34 potential drug regulated aging events. Those events include aging accelerating effects of vandetanib (Caprelsa®) and dasatinib (Sprycel®) in brain and muscle, respectively. Our result also demonstrated aging protective effect of vorinostat (Zolinza®), everolimus (Afinitor®), and bosutinib (Bosulif®) in brain.

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Section: Resultsmentioning

confidence: 99%

A Computational Framework to Characterize the Cancer Drug Induced Effect on Aging Using Transcriptomic Data

et al. 2022

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“…Together, these results suggest that MT alleviates H 2 O 2 -induced oxidative stress by activating the TGF-beta signaling pathway. The mTOR signaling pathway is also related to oxidative stress or antioxidant capacity [ 53 , 54 ]. In this study, ATP6V1C2 was upregulated in MT-treated PTr2 cells and was enriched in the mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Alleviates Oxidative Stress Induced by H2O2 in Porcine Trophectoderm Cells

Chen

Zhao

et al. 2022

Antioxidants

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Placental oxidative stress has been implicated as a main risk factor for placental dysfunction. Alleviation of oxidative stress and enhancement of antioxidant capacity of porcine trophectoderm (PTr2) cells are effective means to maintaining normal placental function. The present study was conducted to evaluate the protective effect of melatonin (MT) on H2O2-induced oxidative damage in PTr2 cells. Our data revealed that pretreatment with MT could significantly improve the decrease in cell viability induced by H2O2, and reduce intracellular reactive oxygen species (ROS) levels and the ratio of apoptotic cells. Here, we compared the transcriptomes of untreated versus melatonin-treated PTr2 cells by RNA-seq analysis and found that differentially expressed genes (DEGs) were highly enriched in the Wnt signaling, TGF-beta signaling and mTOR signaling pathways. Moreover, pretreatment with MT upregulated the antioxidant-related genes such as early growth response3 (EGR3), WAP four-disulfide core domain1 (WFDC1), heme oxygenase1 (HMOX1) and vimentin (VIM). These findings reveal that melatonin protects PTr2 cells from H2O2-induced oxidative stress damage.

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“…These compounds may have implications in CNS therapeutic development. Additionally, mTOR modulators like everolimus and temsirolimus might regulate ROS through mTOR-mediated antioxidant defense [ 215 ]. The mTOR signaling pathway is at the core of many metabolic activities; its activation improves oxidative stress adaptation by activating Nrf2-associated antioxidant signaling [ 216 ].…”

Section: Signaling Pathway Modulators For Cellular Antioxidant Synthesismentioning

confidence: 99%

Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury

Modi,

Musyaju,

Ratcliffe

et al. 2024

Antioxidants

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Traumatic brain injury (TBI) is a major global health problem that affects both civilian and military populations worldwide. Post-injury acute, sub-acute, and chronic progression of secondary injury processes may contribute further to other neurodegenerative diseases. However, there are no approved therapeutic options available that can attenuate TBI-related progressive pathophysiology. Recent advances in preclinical research have identified that mitochondria-centric redox imbalance, bioenergetics failure and calcium dysregulation play a crucial role in secondary injury progression after TBI. Mitochondrial antioxidants play an important role in regulating redox homeostasis. Based on the proven efficacy of preclinical and clinical compounds and targeting numerous pathways to trigger innate antioxidant defense, we may be able to alleviate TBI pathology progression by primarily focusing on preserving post-injury mitochondrial and cerebral function. In this review, we will discuss novel mitochondria-targeted antioxidant compounds, which offer a high capability of successful clinical translation for TBI management in the near future.

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Everolimus, a mammalian target of rapamycin inhibitor, ameliorated streptozotocin-induced learning and memory deficits via neurochemical alterations in male rats

Cited by 10 publications

References 91 publications

A Computational Framework to Characterize the Cancer Drug Induced Effect on Aging Using Transcriptomic Data

A Computational Framework to Characterize the Cancer Drug Induced Effect on Aging Using Transcriptomic Data

Melatonin Alleviates Oxidative Stress Induced by H2O2 in Porcine Trophectoderm Cells

Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury

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