Myricetin slows liquid–liquid phase separation of Tau and activates ATG5-dependent autophagy to suppress Tau toxicity

Abstract

slows liquid-liquid phase separation of Tau and activates ATG5-dependent autophagy to suppress Tau toxicity,

Methylene blue accelerates liquid-to-gel transition of tau condensates impacting tau function and pathology

“…Although cysteine oxidation induced by MB has been proposed to be vital for the inhibitory activity of MB against tau aggregation 15 , 45 , 46 , we found that the redox activity of MB and the cysteine residues of tau are not essential for the MB-promoted tau LLPS or the liquid-to-gel transition of tau droplets. The contrasting activities of MB on tau aggregation and LLPS are unexpected and are distinct from previous reports on other ligands 27 , 48 , 74 – 76 , suggesting that MB may modulate tau aggregation and phase separation through distinct mechanisms.

Fig.

…”

Methylene blue accelerates liquid-to-gel transition of tau condensates impacting tau function and pathology

“…Although cysteine oxidation induced by MB has been proposed to be vital for the inhibitory activity of MB against tau aggregation 15 , 45 , 46 , we found that the redox activity of MB and the cysteine residues of tau are not essential for the MB-promoted tau LLPS or the liquid-to-gel transition of tau droplets. The contrasting activities of MB on tau aggregation and LLPS are unexpected and are distinct from previous reports on other ligands 27 , 48 , 74 – 76 , suggesting that MB may modulate tau aggregation and phase separation through distinct mechanisms.

Fig.

…”

(−)-Epigallocatechin-3-gallate, a Polyphenol from Green Tea, Regulates the Liquid–Liquid Phase Separation of Alzheimer’s-Related Protein Tau

“…Although tau oligomers and aggregates have been widely accepted to be associated with neurodegenerative diseases, − the roles of liquid tau droplets formed by liquid–liquid phase separation (LLPS) in AD progression remain unclear. Recruitment of tubulin into tau droplets promotes the assembly of microtubules. , Furthermore, tau condensates formed on the surface of microtubules regulate microtubule functions. − There is also evidence showing that LLPS of tau may be implicated in tau aggregation and the formation of stress granules. − Interestingly, several tau-binding molecules, including proteins, nucleic acids, organic compounds, and metal ions, regulate LLPS and aggregation of tau simultaneously, ,,− which further supports the close correlation between the LLPS of tau and its aggregation.…”

Hybrid molecules synergistically mitigate ferroptosis and amyloid-associated toxicities in Alzheimer's disease

“…4 H). In the purview of monitoring aberrant tau aggregation in cells, congo red (CR) was used as an inducer of tau aggregation [ [56] , [57] , [58] ]. Treatment with CR (50 μM) led to a significant reduction in cell viability (∼47%) compared to untreated cells.…”

Methylene blue accelerates liquid-to-gel transition of tau condensates impacting tau function and pathology

“…Although cysteine oxidation induced by MB has been proposed to be vital for the inhibitory activity of MB against tau aggregation 15 , 45 , 46 , we found that the redox activity of MB and the cysteine residues of tau are not essential for the MB-promoted tau LLPS or the liquid-to-gel transition of tau droplets. The contrasting activities of MB on tau aggregation and LLPS are unexpected and are distinct from previous reports on other ligands 27 , 48 , 74 – 76 , suggesting that MB may modulate tau aggregation and phase separation through distinct mechanisms.

Fig.

…”

(−)-Epigallocatechin-3-gallate, a Polyphenol from Green Tea, Regulates the Liquid–Liquid Phase Separation of Alzheimer’s-Related Protein Tau

“…Although tau oligomers and aggregates have been widely accepted to be associated with neurodegenerative diseases, − the roles of liquid tau droplets formed by liquid–liquid phase separation (LLPS) in AD progression remain unclear. Recruitment of tubulin into tau droplets promotes the assembly of microtubules. , Furthermore, tau condensates formed on the surface of microtubules regulate microtubule functions. − There is also evidence showing that LLPS of tau may be implicated in tau aggregation and the formation of stress granules. − Interestingly, several tau-binding molecules, including proteins, nucleic acids, organic compounds, and metal ions, regulate LLPS and aggregation of tau simultaneously, ,,− which further supports the close correlation between the LLPS of tau and its aggregation.…”

Hybrid molecules synergistically mitigate ferroptosis and amyloid-associated toxicities in Alzheimer's disease

“…4 H). In the purview of monitoring aberrant tau aggregation in cells, congo red (CR) was used as an inducer of tau aggregation [ [56] , [57] , [58] ]. Treatment with CR (50 μM) led to a significant reduction in cell viability (∼47%) compared to untreated cells.…”

Methylene blue accelerates liquid-to-gel transition of tau condensates impacting tau function and pathology

“…Although cysteine oxidation induced by MB has been proposed to be vital for the inhibitory activity of MB against tau aggregation 15 , 45 , 46 , we found that the redox activity of MB and the cysteine residues of tau are not essential for the MB-promoted tau LLPS or the liquid-to-gel transition of tau droplets. The contrasting activities of MB on tau aggregation and LLPS are unexpected and are distinct from previous reports on other ligands 27 , 48 , 74 – 76 , suggesting that MB may modulate tau aggregation and phase separation through distinct mechanisms.

Fig.

…”

(−)-Epigallocatechin-3-gallate, a Polyphenol from Green Tea, Regulates the Liquid–Liquid Phase Separation of Alzheimer’s-Related Protein Tau

“…Although tau oligomers and aggregates have been widely accepted to be associated with neurodegenerative diseases, − the roles of liquid tau droplets formed by liquid–liquid phase separation (LLPS) in AD progression remain unclear. Recruitment of tubulin into tau droplets promotes the assembly of microtubules. , Furthermore, tau condensates formed on the surface of microtubules regulate microtubule functions. − There is also evidence showing that LLPS of tau may be implicated in tau aggregation and the formation of stress granules. − Interestingly, several tau-binding molecules, including proteins, nucleic acids, organic compounds, and metal ions, regulate LLPS and aggregation of tau simultaneously, ,,− which further supports the close correlation between the LLPS of tau and its aggregation.…”

Hybrid molecules synergistically mitigate ferroptosis and amyloid-associated toxicities in Alzheimer's disease

“…4 H). In the purview of monitoring aberrant tau aggregation in cells, congo red (CR) was used as an inducer of tau aggregation [ [56] , [57] , [58] ]. Treatment with CR (50 μM) led to a significant reduction in cell viability (∼47%) compared to untreated cells.…”