Inhibiting c-Jun N-terminal kinase (JNK)-mediated apoptotic signaling pathway in PC12 cells by a polysaccharide (CCP) from Coptis chinensis against Amyloid-β (Aβ)-induced neurotoxicity

Li, Yujuan; Wang, Bingmei; Liu, Cong; Zhu, Xiaoting; Zhang, Pengqi; Yu, Hongkui; Li, Yunqiang; Li, Zhuohan; Li, Mingquan

doi:10.1016/j.ijbiomac.2019.05.041

Cited by 24 publications

(24 citation statements)

References 37 publications

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“…Recent studies have reported that neuronal oxidative stress destroys mitochondrial membrane permeability and thus causes the release of cytochrome c into the cytosol from mitochondria. Cytosolic cytochrome c activates procaspase-3 to cleaved caspase-3, subsequently resulting in neuronal apoptosis [ 9 , 10 ]. In this aspect, neuronal apoptosis-related protein expression levels of cytosolic cytochrome c and cleaved caspase-3 in the hippocampal tissues of APP/PS1 mice were further analyzed by western blotting.…”

Section: Resultsmentioning

confidence: 99%

“…Seriously, excess ROS cause the oxidative damage of mitochondria and the release of cytochrome c from the mitochondrial membrane into the cytosol. As an apoptosis factor, cytochrome c activates the caspase 3-related apoptosis cascade and triggers the irreversible injury of neurons [ 9 , 10 ]. Therefore, relieving mitochondrial oxidative stress is regarded as a promising therapeutic strategy for AD.…”

Section: Introductionmentioning

confidence: 99%

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Rhein Ameliorates Cognitive Impairment in an APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease by Relieving Oxidative Stress through Activating the SIRT1/PGC-1α Pathway

Yin

Gao

et al. 2022

Oxidative Medicine and Cellular Longevity

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Mitochondrial oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease (AD). Recently, antioxidant therapy has been considered an effective strategy for the treatment of AD. Our previous work discovered that rhein relieved mitochondrial oxidative stress in β-amyloid (Aβ) oligomer-induced primary neurons by improving the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha- (PGC-1α-) regulated mitochondrial biogenesis. While encouraging results have been provided, mechanisms underlying the beneficial effect of rhein on AD are yet to be elucidated in vivo. In this study, we evaluated the therapeutic effect of rhein on an APP/PS1 transgenic (APP/PS1) mouse model of AD and explored its antioxidant mechanisms. As a result, rhein significantly reduced Aβ burden and neuroinflammation and eventually ameliorated cognitive impairment in APP/PS1 mice. Moreover, rhein reversed oxidative stress in the brain of APP/PS1 mice and protected neurons from oxidative stress-associated apoptosis. Further study revealed that rhein promoted mitochondrial biogenesis against oxidative stress by upregulating SIRT1 and its downstream PGC-1α as well as nuclear respiratory factor 1. Improved mitochondrial biogenesis not only increased the activity of superoxide dismutase to scavenge excess reactive oxygen species (ROS) but also repaired mitochondria by mitochondrial fusion to inhibit the production of ROS from the electron transport chain. Notably, the exposure of rhein in the brain analyzed by tissue distribution study indicated that rhein could permeate into the brain to exert its therapeutic effects. In conclusion, these findings drive rhein to serve as a promising therapeutic antioxidant for the treatment of AD. Our research highlights the therapeutic efficacy for AD through regulating mitochondrial biogenesis via the SIRT1/PGC-1α pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rhein Ameliorates Cognitive Impairment in an APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease by Relieving Oxidative Stress through Activating the SIRT1/PGC-1α Pathway

Yin

Gao

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…DL0410, a novel dual cholinesterase inhibitor, protected mouse brains against Aβ‐induced neuronal damage via the Akt/JNK signaling pathway (Zhou et al, 2016). A polysaccharide (CCP) protected cells from Aβ‐induced neurotoxicity by inhibiting JNK‐mediated apoptosis (Li et al, 2019). Therefore, JNK is a potential therapeutic target in AD.…”

Section: Discussionmentioning

confidence: 99%

ErbB4 mediates amyloid β‐induced neurotoxicity through JNK/tau pathway activation: Implications for Alzheimer's disease

Zhang

Zhou

et al. 2021

J of Comparative Neurology

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Accumulation of amyloid β (Aβ) in the brain is a hallmark of Alzheimer's disease (AD). We previously showed that ErbB4 in parvalbumin (PV)‐positive interneurons was associated with Aβ‐induced cognitive deficits; however, the underlying mechanism remains undetermined. Here we found that specific deletion of ErbB4 in PV neurons significantly attenuated oligomeric Aβ‐induced neuronal toxicity and inhibited Aβ‐induced decreases of PSD95 and synaptophysin. Moreover, specific ablation of ErbB4 in PV neurons altered activity‐related protein c‐Fos and decreased hippocampal PV neurons, especially in the dentate gyrus (DG) of hAPP‐J20 mice. Furthermore, c‐Jun N‐terminal kinase (JNK), a protein downstream of ErbB4, was activated by Aβ but not ErbB4's ligand neuregulin 1 (NRG1) β1, suggesting different downstream pathways for Aβ and NRG1β1. JNK phosphorylation was inhibited by the ErbB4 inhibitor AG1478 and by pretreatment with NRG1β1. More importantly, siRNA knockdown of ErbB4 decreased JNK phosphorylation and expression, tau phosphorylation at Ser396 and Thr 205, and Bax expression. Therefore, ErbB4 might mediate Aβ‐induced neuropathology through the JNK/tau pathway and represent a potential therapeutic target in patients with AD.

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“…Our clinical department has used this formula for many years, and this treatment has a significant effect on AD. In a previous study on the mechanism of JDYZF, we found that the extract of Coptis chinensis polysaccharide, the main drug component of JDYZF, improved the lifespan of the transgenic Caenorhabditis elegans CL4176 model of AD, reduced the paralytic rate, inhibited nematode head A β deposition, increased heat shock protein hsp16.2 and hsp16.41 gene expression levels [ 15 ], reduced the A β 25–35 -induced expression of cleaved-caspase-3 and Bax in PC12 cells, increased the expression of Bcl-2 and inhibited apoptosis [ 16 ]. However, the mechanism of JDYZF in the treatment of AD remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Jiedu-Yizhi Formula Improves Cognitive Impairment in an Aβ25–35-Induced Rat Model of Alzheimer’s Disease by Inhibiting Pyroptosis

Wang

Zhu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

Self Cite

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Jiedu-Yizhi formula (JDYZF) is prescribed for the treatment of Alzheimer’s disease (AD) and was created by Jixue Ren, a master of traditional Chinese medicine, based on the “marrow deficiency and toxin damage” theory. In our clinic, this formula has been used for the treatment of AD for many years and has achieved good results. However, the mechanism by which JDYZF improves cognitive impairment has not been determined. In this study, we confirmed that orally administered JDYZF reversed the cognitive deficits in an Aβ25–35-induced rat model, increased the number of neurons in the hippocampal CA1 area, improved their structure, decreased the deposition of β-amyloid (Aβ), reduced the expression of proteins related to the NLRP3/Caspase-1/GSDMD and LPS/Caspase-11/GSDMD pyroptosis pathways, and reduced the levels of interleukin 1β (IL-1β) and IL-18, thereby inhibiting the inflammatory response. In addition, JDYZF exerted no hepatotoxicity in rats. In short, these results provide scientific support for the clinical use of JDYZF to improve the cognitive function of patients with AD.

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Inhibiting c-Jun N-terminal kinase (JNK)-mediated apoptotic signaling pathway in PC12 cells by a polysaccharide (CCP) from Coptis chinensis against Amyloid-β (Aβ)-induced neurotoxicity

Cited by 24 publications

References 37 publications

Rhein Ameliorates Cognitive Impairment in an APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease by Relieving Oxidative Stress through Activating the SIRT1/PGC-1α Pathway

Rhein Ameliorates Cognitive Impairment in an APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease by Relieving Oxidative Stress through Activating the SIRT1/PGC-1α Pathway

ErbB4 mediates amyloid β‐induced neurotoxicity through JNK/tau pathway activation: Implications for Alzheimer's disease

Jiedu-Yizhi Formula Improves Cognitive Impairment in an Aβ25–35-Induced Rat Model of Alzheimer’s Disease by Inhibiting Pyroptosis

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