Fisetin inhibits tau aggregation by interacting with the protein and preventing the formation of β-strands

Xiao, Shifeng; Lu, Yafei; Wu, Qiuping; Yang, Jiaying; Chen, Jierui; Zhong, Suyue; Eliezer, David; Tan, Qiulong; Wu, Chengchen

doi:10.1016/j.ijbiomac.2021.02.210

Cited by 36 publications

(22 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fisetin is recommended to be active therapeutic in many disorders, including neurological diseases, while its role in SAE is still unclear. 16 , 17 , 18 , 19 In this study, we confirmed the neuroprotective effects of fisetin on cognitive deficits caused by SAE. Furthermore, we explored the potential mechanism of fisetin on SAE, which might be relevant to increased mitophagy, scavenged ROS, inactivated NLRP3 inflammasome in CMECs, along with decreased caspase‐1 levels, and reduced secretion of IL‐1β into CNS.…”

Section: Discussionsupporting

confidence: 81%

See 1 more Smart Citation

Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis‐associated encephalopathy

Ding

Chen

et al. 2021

CNS Neurosci Ther

View full text Add to dashboard Cite

Background Fisetin, the effective ingredient of the traditional Chinese medicine named Cotinus coggygria, is recommended to be active therapeutic in many disorders. However, its role in sepsis‐associated encephalopathy (SAE) remains unclarified. Methods Cecal ligation and puncture (CLP) operation was performed to establish a rat model of SAE. Rats were grouped according to the surgery operation and fisetin administration. Cognitive impairment was assessed by Morris water maze test. Disruption of blood‐brain barrier (BBB) integrity was detected by Evan's blue staining. The mitophagy, reactive oxygen species (ROS) generation, NLRP3 inflammasome activation, and pro‐inflammatory cytokines levels were measured through western blot and double immunofluorescence labeling. A transmission electron microscope was applied for the observation of mitochondrial autophagosomes. Results Rats in the CLP group presented increased expression of IL‐1R1, pNF‐κB, TNF‐α, and iNOS in microglial cells, indicating severe inflammation in the central nervous system (CNS). Nevertheless, there was no increase in BBB permeability. Meanwhile, NLRP3 inflammasome was activated in cerebral microvascular endothelial cells (CMECs), presented with an elevation of caspase‐1 expression and IL‐1β secretion into CNS. In addition, we found fisetin significantly improved cognitive dysfunction in rats with SAE. Neuroprotective effects of fisetin might be associated with inhibition of neuroinflammation, represented with decreased expression of IL‐1R1, pNF‐κB, TNF‐α, and iNOS in microglia. Furthermore, fisetin induced mitophagy, scavenged ROS, blocked NLRP3 inflammasome activation of CMECs, as evidenced by decreased expression of caspase‐1 and reduced release of IL‐1β into CNS. Conclusion Collectively, fisetin‐blocked NLRP3 inflammasome activation via promoting mitophagy in CMECs may suppress the secretion of IL‐1β into CNS, reduce neuroinflammation, and contribute to the amelioration of cognitive impairment.

show abstract

Section: Discussionsupporting

confidence: 81%

“…Fisetin is recommended to be active therapeutic in many disorders, including neurological diseases, while its role in SAE is still unclear 16–19 . In this study, we confirmed the neuroprotective effects of fisetin on cognitive deficits caused by SAE.…”

Section: Discussionsupporting

confidence: 80%

Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis‐associated encephalopathy

Ding

Chen

et al. 2021

CNS Neurosci Ther

View full text Add to dashboard Cite

show abstract

“…al investigated the impact of norepinephrine (which has an aromatic moiety) on the tau aggregation by molecular dynamics, and norepinephrine successfully disrupted a part of the tau protein. The same phenomenon was observed with fisetin (with two aromatic cycles), which prevented β-sheet formation, both experimentally and theoretically. Inhibition of tau aggregation was also observed experimentally for other molecules such as proanthocyanidin, purpurin, naphthoquinone-tryptophan, naphthoquinone-dopamine hybrids, and multifunctional 1-(phenylsulfonyl)-1H-indole ligands .…”

Section: Discussionsupporting

confidence: 76%

On the Tracks of the Aggregation Mechanism of the PHF6 Peptide from Tau Protein: Molecular Dynamics, Energy, and Interaction Network Investigations

Fagnen

Giovannini

Catto

et al. 2022

ACS Chem. Neurosci.

View full text Add to dashboard Cite

The formation of neurofibrillary tangles (NFTs), composed of tau protein aggregates, is a hallmark of some neurodegenerative diseases called tauopathies. NFTs are composed of paired helical filaments (PHFs) of tau protein with a dominant βsheet secondary structuration. The NFT formation mechanism is not known yet. This study focuses on PHF6, a crucial hexapeptide responsible for tau aggregation. A 2 μs molecular dynamics simulation was launched to determine the keys of the PHF6 aggregation mechanism. Hydrogen bonding, van der Waals, and other non-covalent interactions as π-stacking were investigated. Parallel aggregation was slightly preferred due to its adaptability, but antiparallel aggregation remained widely present during the PHF6 aggregation. The analysis highlighted the leading role of hydrogen bonds identified at the atomic level for each aggregation process. The aggregation study emphasized the importance of Tyr310 during the β-sheets' complexation through π-stacking.

show abstract

“…Tau K-18 fibril formation decreases neuronal plasticity and promotes neurodegeneration. Fisetin inhibits tau-18 aggregation and neurofibrillary tangles formation ( Xiao et al, 2021 ). Fisetin can also inhibit acetylcholinesterase (AChE) ( Dash et al, 2014 ).…”

Section: Different Neurodegenerative Diseases and The Protective Role...mentioning

confidence: 99%

The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress

et al. 2022

View full text Add to dashboard Cite

Oxidative stress (OS) disrupts the chemical integrity of macromolecules and increases the risk of neurodegenerative diseases. Fisetin is a flavonoid that exhibits potent antioxidant properties and protects the cells against OS. We have viewed the NCBI database, PubMed, Science Direct (Elsevier), Springer-Nature, ResearchGate, and Google Scholar databases to search and collect relevant articles during the preparation of this review. The search keywords are OS, neurodegenerative diseases, fisetin, etc. High level of ROS in the brain tissue decreases ATP levels, and mitochondrial membrane potential and induces lipid peroxidation, chronic inflammation, DNA damage, and apoptosis. The subsequent results are various neuronal diseases. Fisetin is a polyphenolic compound, commonly present in dietary ingredients. The antioxidant properties of this flavonoid diminish oxidative stress, ROS production, neurotoxicity, neuro-inflammation, and neurological disorders. Moreover, it maintains the redox profiles, and mitochondrial functions and inhibits NO production. At the molecular level, fisetin regulates the activity of PI3K/Akt, Nrf2, NF-κB, protein kinase C, and MAPK pathways to prevent OS, inflammatory response, and cytotoxicity. The antioxidant properties of fisetin protect the neural cells from inflammation and apoptotic degeneration. Thus, it can be used in the prevention of neurodegenerative disorders.

show abstract

Fisetin inhibits tau aggregation by interacting with the protein and preventing the formation of β-strands

Cited by 36 publications

References 69 publications

Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis‐associated encephalopathy

Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis‐associated encephalopathy

On the Tracks of the Aggregation Mechanism of the PHF6 Peptide from Tau Protein: Molecular Dynamics, Energy, and Interaction Network Investigations

The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress

Contact Info

Product

Resources

About