Neuroprotection of Triptolide against Amyloid-Beta1-42-induced toxicity via the Akt/mTOR/p70S6K-mediated Autophagy Pathway

Xu, Pengjuan; WU, ZIXUAN; PENG, YANFEI; GAO, JING; Zheng, Fang; Tan, Junzhen; Xu, Jing; WANG, TAO

doi:10.1590/0001-3765202220210938

Cited by 7 publications

(10 citation statements)

References 48 publications

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“…In patients with optic neuritis [165,166], a common occurrence in almost half of patents with MS. APOE serum levels were significantly higher than in control patient groups and the APOE ε3/ε3 genotype may increase the risk of developing optic neuritis in males [167]. In addition to APOE-ε4, MS may share other cellular pathways with AD that lead to cognitive loss such as Aβ [37,102,[168][169][170][171][172]. In studies that examine cerebrospinal fluid biomarkers, changes in Aβ 42 as seen in AD can also predict early cognitive decline in MS [173].…”

Section: Cognitive Loss and Dementia That Can Occur In Multiple Scler...mentioning

confidence: 99%

“…This process of caspase activation and DNA destruction is irreversible [259]. Limiting apoptotic cell death may minimize memory loss and cognition during both acute and chronic insults [34,93,96,169,172,185,276,279]. This may occur during measures that reduce inflammatory pathways and affect neuronal and oligodendrocyte survival [9,108,132,187,252,276,[279][280][281][282], as well as cognitive performance [25,[283][284][285].…”

Section: Autophagy Apoptosis Pyroptosis and Ferroptosis Involvement I...mentioning

confidence: 99%

“…mTOR can influence programmed cell death pathways through multiple mechanisms. mTOR activity can block apoptotic cell death in the nervous system [15,69,71,73,85,115,172,276,407], prevent oxidative stress injury [399,[408][409][410], modulate the progression of infectious agents [85,[411][412][413][414][415][416], and oversee metabolic homeostasis [72,115,417,418]. In the presence of mTOR activity, Aβ toxicity can be blocked [154,172,399,409,[419][420][421], vascular cell death is prevented [105,422], and neonatal and adult central nervous system hypoxic injury is prevented [276,423].…”

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

“…mTOR activity can block apoptotic cell death in the nervous system [15,69,71,73,85,115,172,276,407], prevent oxidative stress injury [399,[408][409][410], modulate the progression of infectious agents [85,[411][412][413][414][415][416], and oversee metabolic homeostasis [72,115,417,418]. In the presence of mTOR activity, Aβ toxicity can be blocked [154,172,399,409,[419][420][421], vascular cell death is prevented [105,422], and neonatal and adult central nervous system hypoxic injury is prevented [276,423]. Furthermore, neuronal differentiation is promoted [424], microglia survival is increased during oxidative stress exposure and Aβ toxicity [117,399,409,420,425,426], and neuroplasticity is fostered [48,310,427,…”

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

“…Autophagy pathways are also critical for impacting neurodegeneration and usually involve the blockade of mTOR activity for neuroprotective pathways [17,22,44,70,100,105,169,[242][243][244]259,293]. The induction of autophagy, which may require an mTOR blockade, can protect neuronal and non-neuronal cells [10,24,73,89,106,172,224,442]. For example, diseases of the retina may require mTOR inhibition with rapamycin to prevent retinal degeneration during MS DM [46].…”

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

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Cognitive Impairment in Multiple Sclerosis

Maiese

2023

Bioengineering

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Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in the nervous system with increased prevalence over the last five decades, and is now being recognized as one significant etiology of cognitive loss and dementia. Presently, disease modifying therapies can limit the rate of relapse and potentially reduce brain volume loss in patients with MS, but unfortunately cannot prevent disease progression or the onset of cognitive disability. Innovative strategies are therefore required to address areas of inflammation, immune cell activation, and cell survival that involve novel pathways of programmed cell death, mammalian forkhead transcription factors (FoxOs), the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and associated pathways with the apolipoprotein E (APOE-ε4) gene and severe acute respiratory syndrome coronavirus (SARS-CoV-2). These pathways are intertwined at multiple levels and can involve metabolic oversight with cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into the mechanisms of these pathways can provide new avenues of discovery for the therapeutic treatment of dementia and loss in cognition that occurs during MS.

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Section: Cognitive Loss and Dementia That Can Occur In Multiple Scler...mentioning

confidence: 99%

Section: Autophagy Apoptosis Pyroptosis and Ferroptosis Involvement I...mentioning

confidence: 99%

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

See 3 more Smart Citations

Cognitive Impairment in Multiple Sclerosis

Maiese

2023

Bioengineering

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Triptolide activates the Nrf2 signaling pathway and inhibits the NF-κB signaling pathway to improve Alzheimer disease

He,

Botchway,

Zhang

et al. 2023

Metab Brain Dis

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Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future

Zhang

Chen

et al. 2023

Sig Transduct Target Ther

166

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Amyloid β protein (Aβ) is the main component of neuritic plaques in Alzheimer’s disease (AD), and its accumulation has been considered as the molecular driver of Alzheimer’s pathogenesis and progression. Aβ has been the prime target for the development of AD therapy. However, the repeated failures of Aβ-targeted clinical trials have cast considerable doubt on the amyloid cascade hypothesis and whether the development of Alzheimer’s drug has followed the correct course. However, the recent successes of Aβ targeted trials have assuaged those doubts. In this review, we discussed the evolution of the amyloid cascade hypothesis over the last 30 years and summarized its application in Alzheimer’s diagnosis and modification. In particular, we extensively discussed the pitfalls, promises and important unanswered questions regarding the current anti-Aβ therapy, as well as strategies for further study and development of more feasible Aβ-targeted approaches in the optimization of AD prevention and treatment.

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Neuroprotection of Triptolide against Amyloid-Beta1-42-induced toxicity via the Akt/mTOR/p70S6K-mediated Autophagy Pathway

Cited by 7 publications

References 48 publications

Cognitive Impairment in Multiple Sclerosis

Cognitive Impairment in Multiple Sclerosis

Triptolide activates the Nrf2 signaling pathway and inhibits the NF-κB signaling pathway to improve Alzheimer disease

Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future

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