Toxicities of amyloid-beta and tau protein are reciprocally enhanced in the Drosophila model

Wu, Jiarui; Zhou, Bing; Huang, Yunpeng; Sun, Zhendong; Hu, Jiaxin

doi:10.4103/1673-5374.336872

Cited by 5 publications

(3 citation statements)

References 76 publications

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“…Lowering total tau levels were not only capable of preventing and reversing tau pathology, but cell survival was also significantly extended and neuronal loss abrogated [ 105 ]. High tau levels not only promote its own aggregation but can also mediate the toxicity of Aβ 42 [ 19 , 20 , 22 , 106 , 107 ]. In relation to this, it has been demonstrated that tau reduction by gene knockout could hinder Aβ-induced deficits in axonal transport [ 108 ] and ameliorate the cognitive defects in mice models without influencing baseline neuronal functions [ 109 ].…”

Section: Discussionmentioning

confidence: 99%

“…Brains from AD patients show distinct histopathological hallmarks which are extracellular deposits of Aβ peptides in the form of senile plaques, Aβ deposits in the cerebral blood vessels, and intracellular inclusion of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein [ 18 ]. Regarding the formation of Aβ deposits and NFTs, findings concerning which comes first are discordant; however, growing evidence recognizes the very early onset of tau pathology and its key role in mediating Aβ toxicity [ 19 , 20 , 21 , 22 ]. It was therefore suggested that total and phosphorylated tau accumulation may be pathologically more relevant than Aβ plaques to the development of neurodegeneration and cognitive decline in AD patients.…”

Section: Introductionmentioning

confidence: 99%

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24-Hydroxycholesterol Induces Tau Proteasome-Dependent Degradation via the SIRT1/PGC1α/Nrf2 Pathway: A Potential Mechanism to Counteract Alzheimer’s Disease

et al. 2023

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Considerable evidence indicates that cholesterol oxidation products, named oxysterols, play a key role in several events involved in Alzheimer’s disease (AD) pathogenesis. Although the majority of oxysterols causes neuron dysfunction and degeneration, 24-hydroxycholesterol (24-OHC) has recently been thought to be neuroprotective also. The present study aimed at supporting this concept by exploring, in SK-N-BE neuroblastoma cells, whether 24-OHC affected the neuroprotective SIRT1/PGC1α/Nrf2 axis. We demonstrated that 24-OHC, through the up-regulation of the deacetylase SIRT1, was able to increase both PGC1α and Nrf2 expression and protein levels, as well as Nrf2 nuclear translocation. By acting on this neuroprotective pathway, 24-OHC favors tau protein clearance by triggering tau ubiquitination and subsequently its degradation through the ubiquitin–proteasome system. We also observed a modulation of SIRT1, PGC1α, and Nrf2 expression and synthesis in the brain of AD patients with the progression of the disease, suggesting their potential role in neuroprotection. These findings suggest that 24-OHC contributes to tau degradation through the up-regulation of the SIRT1/PGC1α/Nrf2 axis. Overall, the evidence points out the importance of avoiding 24-OHC loss, which can occur in the AD brain, and of limiting SIRT1, PGC1α, and Nrf2 deregulation in order to prevent the neurotoxic accumulation of hyperphosphorylated tau and counteract neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

24-Hydroxycholesterol Induces Tau Proteasome-Dependent Degradation via the SIRT1/PGC1α/Nrf2 Pathway: A Potential Mechanism to Counteract Alzheimer’s Disease

et al. 2023

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“…Existing studies have shown that general anesthetics (such as isoflurane and propofol) can enhance Aβ protein oligomerization and synthesis and τ protein phosphorylation. 24 Extracellular aggregation of Aβ into oligomers can increase its neurotoxicity and induce neuronal degeneration and even apoptosis. 25 Multiple kinases hyperphosphorylate the τ protein.…”

Section: Discussionmentioning

confidence: 99%

Effect of Repeated Intranasal Administration of Different Doses of Insulin on Postoperative Delirium, Serum τ and Aβ Protein in Elderly Patients Undergoing Radical Esophageal Cancer Surgery

Huang¹,

Shi²,

Yi³

et al. 2023

NDT

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Objective Postoperative delirium is common after general anesthesia in older patients. However, there are currently no effective preventive measures. This study investigated the effect of repeated intranasal administration of different insulin doses before surgery on postoperative delirium in older patients with esophageal cancer, and the possible mechanism for its efficacy. Methods In this randomized, placebo-controlled, double-blind, parallel-group study, 90 older patients were randomly assigned to either a Control (normal saline), Insulin 1 (20 U/0.5 mL intranasal insulin), or Insulin 2 (30 U/0.75 mL intranasal insulin) group. Delirium was assessed on postoperative days 1 (T2), 2 (T3), and 3 (T4) using the Confusion Assessment Method for the Intensive Care Unit. Serum τ and Aβ protein levels were measured at T0 (before insulin/saline administration), T1 (end of surgery), T2, T3 and T4. Results The Insulin 2 group had a significantly lower prevalence of delirium compared to the Control and Insulin 1 groups three days after surgery. Compared to baseline, τ and Aβ protein levels increased significantly at T1–T4. Compared to the Control group, the Insulin 1 and 2 groups had significantly lower τ and Aβ protein levels at T1–T4, and the Insulin 2 group had significantly lower levels than the Insulin 1 group at T1–T2. Conclusion The administration of 30 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can significantly reduce postoperative delirium in older patients undergoing radical esophagectomy. It can also decrease postoperative τ and Aβ protein expression without causing hypoglycemia. Clinical Trial Registration This study was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn , with the unique identifier: ChiCTR2100054245; December 11, 2021).

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Strategies for measuring concentrations and forms of amyloid-β peptides

Shen,

Liu,

Kong

et al. 2024

Biosensors and Bioelectronics

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Toxicities of amyloid-beta and tau protein are reciprocally enhanced in the Drosophila model

Cited by 5 publications

References 76 publications

24-Hydroxycholesterol Induces Tau Proteasome-Dependent Degradation via the SIRT1/PGC1α/Nrf2 Pathway: A Potential Mechanism to Counteract Alzheimer’s Disease

24-Hydroxycholesterol Induces Tau Proteasome-Dependent Degradation via the SIRT1/PGC1α/Nrf2 Pathway: A Potential Mechanism to Counteract Alzheimer’s Disease

Effect of Repeated Intranasal Administration of Different Doses of Insulin on Postoperative Delirium, Serum τ and Aβ Protein in Elderly Patients Undergoing Radical Esophageal Cancer Surgery

Strategies for measuring concentrations and forms of amyloid-β peptides

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