Autophagy: a double-edged sword for neuronal survival after cerebral ischemia

Chen, Wenqi; Sun, Yinyi; Liu, Kangyong; Sun, Xiaojiang

doi:10.4103/1673-5374.135329

Cited by 142 publications

(43 citation statements)

References 72 publications

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“…However, emerging evidence indicated that the self‐cannibalistic function may be associated with excessive cell death under certain conditions31, 32 Therefore, more and more scholars described the role of autophagy in various pathophysiological processes as a double‐edged sword 33, 34, 35, 36. From the previous study, the autophagy was proved to be a protective role for AKI37, 38 .…”

Section: Discussionmentioning

confidence: 99%

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Zhou

Fan

Zhong

et al. 2018

J Cellular Molecular Medi

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The ability of cisplatin (cis‐diamminedichloroplatinum II) toxicity to induce acute kidney injury (AKI) has attracted people's attention and concern for a long time, but its molecular mechanisms are still widely unknown. We found that the expression of transforming growth factor‐β (TGF‐β)‐activated kinase 1 (TAK1) could be increased in kidneys of mice administrated with cisplatin. Autophagy is an evolutionarily conserved catabolic pathway and is involved in various acute and chronic injuries. Moreover, p38 MAPK (mitogen‐activated protein kinase) and ERK regulate autophagy in response to various stimuli. Therefore, our hypothesis is that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells and thus exacerbating kidney damage. Here, BALB/c mice were intraperitoneally injected with a TAK1 inhibitor and were then administrated with sham or cisplatin at 20 mg/kg by intraperitoneal injection. Compared with mice in the vehicle cisplatin group, mice intraperitoneally injected with a TAK1 inhibitor were found to have lower serum creatinine and less tubular damage following cisplatin‐induced AKI. Furthermore, inhibition of TAK1 reduced p38 and Erk phosphorylation, decreased expression of LC3II and reversed the down‐regulation of P62 expression induced by cisplatin. The hypothesis was verified with tubular epithelial cells administrated with cisplatin in vitro. Finally, p38 inhibitor or ERK inhibitor abated autophagy activation and cell viability reduction in tubular epithelial cells treated with cisplatin plus TAK1 overexpression vector. Taken together, our results show that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells that exacerbates kidney damage.

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Section: Discussionmentioning

confidence: 99%

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Zhou

Fan

Zhong

et al. 2018

J Cellular Molecular Medi

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“…Stroke results in multiple complications that can affect the economic welfare and daily function of individuals [10,11]. Cerebral ischemic disease is one of the five leading causes of death that also includes cardiac disease, cancer, chronic lower respiratory disease, and trauma [12].…”

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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“…In regards to autophagy during DM, this pathway of programmed cell death may have variable outcomes (141). Autophagy recycles cytoplasmic components and discards defective organelles for tissue remodeling (125, 142).…”

Section: Dm Apoptosis and Autophagymentioning

confidence: 99%

“…However, it should be noted that autophagy might not be consistently beneficial (128, 141, 146). Under some conditions, autophagy may be less of a prominent modulator of cell survival than apoptosis in some experimental models (147).…”

Section: Dm Apoptosis and Autophagymentioning

confidence: 99%

Programming Apoptosis and Autophagy with Novel Approaches for Diabetes Mellitus

Maiese¹

2015

CNR

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According to the World Health Organization, diabetes mellitus (DM) in the year 2030 will be ranked the seventh leading cause of death in the world. DM impacts all systems of the body with oxidant stress controlling cell fate through endoplasmic reticulum stress, mitochondrial dysfunction, alterations in uncoupling proteins, and the induction of apoptosis and autophagy. Multiple treatment approaches are being entertained for DM with Wnt1 inducible signaling pathway protein 1 (WISP1), mechanistic target of rapamycin (mTOR), and silent mating type information regulation 2 homolog) 1 (S. cerevisiae) (SIRT1) generating significant interest as target pathways that can address maintenance of glucose homeostasis as well as prevention of cellular pathology by controlling insulin resistance, stem cell proliferation, and the programmed cell death pathways of apoptosis and autophagy. WISP1, mTOR, and SIRT1 can rely upon similar pathways such as AMP activated protein kinase as well as govern cellular metabolism through cytokines such as EPO and oral hypoglycemics such as metformin. Yet, these pathways require precise biological control to exclude potentially detrimental clinical outcomes. Further elucidation of the ability to translate the roles of WISP1, mTOR, and SIRT1 into effective clinical avenues offers compelling prospects for new therapies against DM that can benefit hundreds of millions of individuals throughout the globe.

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Autophagy: a double-edged sword for neuronal survival after cerebral ischemia

Cited by 142 publications

References 72 publications

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Charting a course for erythropoietin in traumatic brain injury

Programming Apoptosis and Autophagy with Novel Approaches for Diabetes Mellitus

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