Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders

Maiese, Kenneth

doi:10.1111/bcp.12804

Cited by 159 publications

(126 citation statements)

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“…In contrast, once the destruction of cellular DNA occurs, it is usually not considered to be completely reversible (59). Apoptosis in the nervous system can be involved in retinal degeneration (24, 76), pain sensitivity and neuronal injury (77), Aβ injury (13, 78–82), epilepsy (83, 84), Parkinson’s disease (11, 41, 85–87), diabetic injury (14, 17, 26, 88–90), traumatic brain injury (41, 91–93), and autism (94). …”

Section: Autophagy and Apoptosismentioning

confidence: 99%

“…These neural aggregates lead to behavior impairments that can be resolved with the maintenance of autophagy pathways in neurons (99). In addition, autophagy is involved in a number of degenerative disorders such as cognitive decline (14, 56, 100), AD (40, 48, 83, 101, 102), Parkinson’s disease (11, 87, 98, 103), Huntington’s disease (59, 104, 105), DM (14, 17, 40, 89, 106, 107), and aging processes (8, 40, 85, 91, 108–111). Autophagy also may be required to preserve metabolic homeostasis with mTOR (112).…”

Section: Autophagy and Apoptosismentioning

confidence: 99%

“…SIRT1 pathways are involved in vascular survival and senescence (88, 152, 161), atherosclerosis (162–166), lifespan extension (4, 167–169), diabetic retinopathy (170), cellular metabolism and DM (14, 17, 20, 115, 145, 171, 172), oxidative stress pathways (58, 148, 173–179), and neuronal survival and cognition (11, 113, 180–183). …”

Section: Sirt1 and Non-coding Rnasmentioning

confidence: 99%

“…Interestingly, neurodegenerative disorders form a significant component of NCDs (11). Neurodegenerative disorders include more than six hundred disease entities and progressively lead to nervous system dysfunction (12).…”

Section: Introductionmentioning

confidence: 99%

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

Maiese¹

2018

CNR

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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.

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Section: Autophagy and Apoptosismentioning

confidence: 99%

Section: Autophagy and Apoptosismentioning

confidence: 99%

Section: Sirt1 and Non-coding Rnasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Maiese¹

2018

CNR

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“…Chronic neurodegenerative diseases, such as Parkinson's disease (PD) [3,4], can affect approximately 4 percent of individuals over the age of sixty. In addition, the number of individuals with PD is expected to double by the year 2030.…”

Section: Erythropoietin and Traumatic Brain Injury: Translating Expermentioning

confidence: 99%

Charting a course for erythropoietin in traumatic brain injury

Maiese¹

2016

J Transl Sci

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Traumatic brain injury (TBI) is a severe public health problem that impacts more than four million individuals in the United States alone and is increasing in incidence on a global scale. Importantly, TBI can result in acute as well as chronic impairments for the nervous system leaving individuals with chronic disability and in instances of severe trauma, death becomes the ultimate outcome. In light of the significant negative health consequences of TBI, multiple therapeutic strategies are under investigation, but those focusing upon the cytokine and growth factor erythropoietin (EPO) have generated a great degree of enthusiasm. EPO can control cell death pathways tied to apoptosis and autophagy as well oversees processes that affect cellular longevity and aging. In vitro studies and experimental animal models of TBI have shown that EPO can restore axonal integrity, promote cellular proliferation, reduce brain edema, and preserve cellular energy homeostasis and mitochondrial function. Clinical studies for neurodegenerative disorders that involve loss of cognition or developmental brain injury support a positive role for EPO to prevent or reduce injury in the nervous system. However, recent clinical trials with EPO and TBI have not produced such clear conclusions. Further clinical studies are warranted to address the potential efficacy of EPO during TBI, the concerns with the onset, extent, and duration of EPO therapeutic strategies, and to focus upon the specific downstream pathways controlled by EPO such as protein kinase B (Akt), mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), sirtuins, wingless pathways, and forkhead transcription factors for improved precision against the detrimental effects of TBI. KeywordsAkt; Alzheimer's disease; apoptosis; autophagy; erythropoietin; forkhead; mTOR; Parkinson's disease; neurodegeneration; programmed cell death; sirtuins; traumatic brain injury; Wnt Erythropoietin and traumatic brain injury: Translating experimental success into clinical efficacyIn more than 30 million individuals throughout the world, both acute and chronic neurodegenerative disorders can result in significant disability as well as eventual death [1,2]. Chronic neurodegenerative diseases, such as Parkinson's disease (PD) [3,4], can affect approximately 4 percent of individuals over the age of sixty. In addition, the number ofThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For the sporadic form of AD, approximately 10 percent of the global population over the age of sixty-five is affected [3,5]. Over the next two decades, it is estimated that the number of those suffering from AD will increase significantly to more than 30 million individuals [6][7][8]. HHS Public AccessFor acute neurodegenerative injury, disorders such as stroke can impact almost 800,000 individuals every year with a...

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Retracted:Propofol exerts neuroprotective functions by down‐regulating microRNA‐19a in glutamic acid‐induced PC12 cells

Xin

Jiang

et al. 2020

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Background: Propofol, a kind of intravenous sedative drug, is certified that exerts anti-inflammation and antitumor functions. However, the influence of propofol in cerebral injury and the corresponding mechanism remains unexplained, that our article focuses on. Methods: PC12 cells were treated with propofol and exposed in glutamic acid (Glu) solutions. Cell viability, apoptotic potential, apoptosis-related and autophagy-linked proteins were tested via CCK-8, flow cytometry, and western blot assays. Reverse transcription-quantitative real-time PCR was utilized to test miR-19a expression in Glu-stimulated cells. Next, miR-19a mimic transfection was used to assess the effects of miR-19a on cell apoptosis and autophagy in Glu or propofol treated cells. Finally, western blot was performed to test AMPK and mTOR pathways. Results: Glu exposure promoted cell apoptosis and autophagy of PC12 cells, while propofol attenuated cell apoptosis and autophagy triggered by Glu. Additionally, propofol decreased the miR-19a expression in Glu-stimulated PC12 cells. Meanwhile, over-expression of miR-19a reversed the effects of propofol on Gluinduced cell apoptosis and autophagy. Moreover, propofol potentiated AMPK and mTOR pathways in Glu-stimulated PC12 cells via impeding miR-19a expression. Conclusions: These finding revealed that propofol relieved Glu-triggered apoptosis and autophagy of PC12, and activated AMPK and mTOR pathways by suppressing miR-19a expression.

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Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders

Cited by 159 publications

References 272 publications

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

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

Charting a course for erythropoietin in traumatic brain injury

Retracted:Propofol exerts neuroprotective functions by down‐regulating microRNA‐19a in glutamic acid‐induced PC12 cells

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