The mammalian target of rapamycin(m TOR) pathway is abnormally activated in lung cancer.However, the anti-lung cancer effect of m TOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an a...The mammalian target of rapamycin(m TOR) pathway is abnormally activated in lung cancer.However, the anti-lung cancer effect of m TOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the m TOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2(labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. EveRh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased cMYC mediated the accumulation of tribbles homolog 3(TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.展开更多
Parkinson＇s disease （PD） is the second most common neurodegenerative disorder and is characterized by its progressive course. The current therapies are aimed at alleviating symptoms by rescuing the unbalanced physi...Parkinson＇s disease （PD） is the second most common neurodegenerative disorder and is characterized by its progressive course. The current therapies are aimed at alleviating symptoms by rescuing the unbalanced physiological dopamine metabolism and recovery of damaged neuronal circuits. However, these strategies result in insufficient clinical benefits for many patients and fail to halt disease progression. Therefore, new therapeutic targets could serve as the gateway against PD degeneration. One pathological hallmark of PD is the formation of intracytoplasmic protein inclusions or Lewy bodies, in neurons. Recent studies have suggested that Lewy bodies are formed similarly to aggresomes, and results have supported the concept that the novel cellular organelle, the aggresome, is a cytoprotective response that sequesters and facilitates clearance of potentially toxic protein aggregates. In addition, a-tubulin deacetylase has been shown to regulate aggresome formation and rescue neural cell viability in response to misfolded protein. Therefore, the regulation of aggresome formation to trigger cellular self-protection system could arrest PD progression. The present study discusses research progress related to Lewy bodies, aggresomes, and histone deacetylases, with an emphasis on histone deacetylase 6 and sirtuin type 2.展开更多
Parkinson's disease(PD)is diagnosed when patients exhibit bradykinesia with tremor and/or rigidity,and when these symptoms respond to dopaminergic medications.Yet in the last years there was a greater recognition ...Parkinson's disease(PD)is diagnosed when patients exhibit bradykinesia with tremor and/or rigidity,and when these symptoms respond to dopaminergic medications.Yet in the last years there was a greater recognition of additional aspects of the disease including non-motor symptoms and prodromal states with associated pathology in various regions of the nervous system.In this review we discuss current concepts of two major alterations found during the course of the disease:cytoplasmic aggregates of the protein a-synuclein and the degeneration of dopaminergic neurons.We provide an overview of new approaches in this field based on current concepts and latest literature.In many areas,translational research on PD has advanced the understanding of the disease but there is still a need for more effective therapeutic options based on the insights into the basic biological phenomena.展开更多
基金supported by the National Natural Science Foundation of China(No.81973516)partially supported by the Science and Technology Development Fund,Macao S.A.R,China(Nos.024/2016/A1 and 0129/2019/A3)University of Macao(No.CPG2021-00022-ICMS)。
文摘The mammalian target of rapamycin(m TOR) pathway is abnormally activated in lung cancer.However, the anti-lung cancer effect of m TOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the m TOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2(labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. EveRh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased cMYC mediated the accumulation of tribbles homolog 3(TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.
文摘Parkinson＇s disease （PD） is the second most common neurodegenerative disorder and is characterized by its progressive course. The current therapies are aimed at alleviating symptoms by rescuing the unbalanced physiological dopamine metabolism and recovery of damaged neuronal circuits. However, these strategies result in insufficient clinical benefits for many patients and fail to halt disease progression. Therefore, new therapeutic targets could serve as the gateway against PD degeneration. One pathological hallmark of PD is the formation of intracytoplasmic protein inclusions or Lewy bodies, in neurons. Recent studies have suggested that Lewy bodies are formed similarly to aggresomes, and results have supported the concept that the novel cellular organelle, the aggresome, is a cytoprotective response that sequesters and facilitates clearance of potentially toxic protein aggregates. In addition, a-tubulin deacetylase has been shown to regulate aggresome formation and rescue neural cell viability in response to misfolded protein. Therefore, the regulation of aggresome formation to trigger cellular self-protection system could arrest PD progression. The present study discusses research progress related to Lewy bodies, aggresomes, and histone deacetylases, with an emphasis on histone deacetylase 6 and sirtuin type 2.
基金by the German Research Foundation(DFG,FA 658/3-1).
文摘Parkinson's disease(PD)is diagnosed when patients exhibit bradykinesia with tremor and/or rigidity,and when these symptoms respond to dopaminergic medications.Yet in the last years there was a greater recognition of additional aspects of the disease including non-motor symptoms and prodromal states with associated pathology in various regions of the nervous system.In this review we discuss current concepts of two major alterations found during the course of the disease:cytoplasmic aggregates of the protein a-synuclein and the degeneration of dopaminergic neurons.We provide an overview of new approaches in this field based on current concepts and latest literature.In many areas,translational research on PD has advanced the understanding of the disease but there is still a need for more effective therapeutic options based on the insights into the basic biological phenomena.
