Temporal changes in mammalian target of rapamycin (mTOR) and phosphorylated-mTOR expressions in the hippocampal CA1 region of rat with vascular dementia

Park, Jina; Lee, Choong‐Hyun

doi:10.4142/jvs.2017.18.1.11

Cited by 23 publications

(19 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been well known that CCH can lead to cognitive impairment as well as neuropathological alterations in some brain regions including hippocampus and cerebral white matter ( Farkas et al ., 2004 , 2007 ; Yang et al ., 2014 ; Ueno et al ., 2015 ; Lee et al ., 2016a ). Especially, among some brain regions, the hippocampal CA1 region is thought to be one of the most vulnerable region following CCH ( Farkas et al ., 2004 ; Cechetti et al ., 2012 ; Lee et al ., 2016a ; Park and Lee, 2016 ). Some of underlying mechanisms, which related to the CCH-induced hippocampal neuronal damage, have been suggested to include oxidative stress and neuroinflammation ( Cechetti et al ., 2012 ; He et al ., 2012 ; Qu et al ., 2014 ; Lee et al ., 2016a ).…”

Section: Introductionmentioning

confidence: 99%

“…Some of underlying mechanisms, which related to the CCH-induced hippocampal neuronal damage, have been suggested to include oxidative stress and neuroinflammation ( Cechetti et al ., 2012 ; He et al ., 2012 ; Qu et al ., 2014 ; Lee et al ., 2016a ). In addition, recent studies reported that a significant alterations of the mammalian target of rapamycin (mTOR) signaling pathway, such as decrease of phosphorylated mTOR (p-mTOR), occurred in the hippocampus following CCH ( Jia et al ., 2015 ; Park and Lee, 2016 ). However, the precise mechanisms about CCH-induced neuronal damage have not been fully elucidated yet.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neuroprotective Effect of Duloxetine on Chronic Cerebral Hypoperfusion-Induced Hippocampal Neuronal Damage

Park

Lee

2018

Biomolecules & Therapeutics

Self Cite

View full text Add to dashboard Cite

Chronic cerebral hypoperfusion (CCH), which is associated with onset of vascular dementia, causes cognitive impairment and neuropathological alterations in the brain. In the present study, we examined the neuroprotective effect of duloxetine (DXT), a potent and balanced serotonin/norepinephrine reuptake inhibitor, on CCH-induced neuronal damage in the hippocampal CA1 region using a rat model of permanent bilateral common carotid arteries occlusion. We found that treatment with 20 mg/kg DXT could attenuate the neuronal damage, the reduction of phosphorylations of mTOR and p70S6K as well as the elevations of TNF-α and IL-1β levels in the hippocampal CA1 region at 28 days following CCH. These results indicate that DXT displays the neuroprotective effect against CCH-induced hippocampal neuronal death, and that neuroprotective effect of DXT may be closely related with the attenuations of CCH-induced decrease of mTOR/p70S6K signaling pathway as well as CCH-induced neuroinflammatory process.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Duloxetine on Chronic Cerebral Hypoperfusion-Induced Hippocampal Neuronal Damage

Park

Lee

2018

Biomolecules & Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…mTOR can oversee multiple physiologic and disease processes such as cellular metabolism (69, 70), bone formation (71-73), diabetes (35, 43, 74-77), neurodegenerative disorders (37, 78-83), dementia (12, 84-86), and cancer (25, 27, 87-91). In addition, mTOR has a significant role in the modulation of autophagy induction (92).…”

Section: Circadian Rhythm Mtor and Sirt1mentioning

confidence: 99%

Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer

Maiese¹

2017

CNR

View full text Add to dashboard Cite

Background The mammalian circadian clock and its associated clock genes are increasingly be recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. Methods In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis. Results In experimental models, lifespan is significantly reduced with the introduction of arrhythmic mutants and leads to an increase in oxidative stress exposure. Interestingly, patients with Alzheimer's disease and Parkinson's disease may suffer disease onset or progression as a result of alterations in the DNA methylation of clock genes as well as prolonged pharmacological treatment for these disorders that may lead to impairment of circadian rhythm function. Tumorigenesis also can occur with the loss of a maintained circadian rhythm and lead to an increased risk for nasopharyngeal carcinoma, breast cancer, and metastatic colorectal cancer. Interestingly, the circadian clock system relies upon the regulation of the critical pathways of autophagy, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) as well as proliferative mechanisms that involve the wingless pathway of Wnt/β-catenin pathway to foster cell survival during injury and block tumor cell growth. Conclusions Future targeting of the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm may hold the key for the development of novel and effective therapies against aging- related disorders, neurodegenerative disease, and tumorigenesis.

show abstract

“…AD is not the result of a single etiology (42). Multiple mechanisms may lead to cognitive impairment and involve cellular injury from β-amyloid (Aβ), tau, excitotoxicity, mitochondrial damage, acetylcholine loss, astrocytic cell injury, oxidative stress, and cellular metabolic dysfunction with DM (14, 51–57). Yet, there is a growing arsenal of novel therapeutic strategies directed against AD and other neurodegenerative disorders that include circadian rhythm clock genes (9), non-coding ribonucleic acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs) (56, 58, 59).…”

Section: Novel Nervous System Strategiesmentioning

confidence: 99%

“…mTOR also is known as the mammalian target of rapamycin and the FK506-binding protein 12-rapamycin complex-associated protein 1. mTOR controls multiple functions that determine the transcription of genes, proliferation and senescence of cells, protein formation, cellular metabolism, and cellular longevity (9, 57, 77, 129, 130). Melatonin, a pineal hormone that controls circadian rhythm, relies upon autophagy pathways and mTOR to control processes of aging and neurodegeneration (131).…”

Section: Circadian Clock Genesmentioning

confidence: 99%

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

Maiese¹

2018

CNR

View full text Add to dashboard Cite

BACKGROUND With the global increase in life span expectancy, neurodegenerative disorders continue to affect an ever increasing number of individuals throughout the world. New treatment strategies for neurodegenerative diseases are desperately required given the lack of current treatment modalities. METHODS Here we examine novel strategies for neurodegenerative disorders that include circadian clock genes, non-coding ribonucleic acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs). RESULTS Circadian clock genes, non-coding RNAs, and FoxOs offer exciting prospects to potentially limit or remove the significant disability and death associated with neurodegenerative disorders. Each of these pathways have an intimate relationship with the programmed death pathways of autophagy and apoptosis and share a common link to the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) and the mechanistic target of rapamycin (mTOR). Circadian clock genes are necessary to modulate autophagy, limit cognitive loss, and prevent neuronal injury. Non-coding RNAs can control neuronal stem cell development and neuronal differentiation and offer protection against vascular disease such as atherosclerosis. FoxOs provide exciting prospects to block neuronal apoptotic death and to activate pathways of autophagy to remove toxic accumulations in neurons that can lead to neurodegenerative disorders. CONCLUSIONS Continued work with circadian clock genes, non-coding RNAs, and FoxOs can offer new prospects and hope for the development of vital strategies for the treatment of neurodegenerative diseases. These innovative investigative avenues have the potential to significantly limit disability and death from these devastating disorders.

show abstract

Temporal changes in mammalian target of rapamycin (mTOR) and phosphorylated-mTOR expressions in the hippocampal CA1 region of rat with vascular dementia

Cited by 23 publications

References 29 publications

Neuroprotective Effect of Duloxetine on Chronic Cerebral Hypoperfusion-Induced Hippocampal Neuronal Damage

Neuroprotective Effect of Duloxetine on Chronic Cerebral Hypoperfusion-Induced Hippocampal Neuronal Damage

Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

Contact Info

Product

Resources

About