HDAC6 ZnF UBP as the Modifier of Tau Structure and Function

Area of Science:

• Biochemistry
• Molecular Biology
• Neuroscience

Background:

• Histone deacetylase 6 (HDAC6) is a class II deacetylase regulating cellular functions via deacetylation.
• HDAC6 possesses unique domains, including a zinc-finger ubiquitin-binding protein (ZnF UBP) domain, distinct from other HDACs.
• HDAC6 influences cellular processes by modifying microtubules, HSP90, and cortactin.

Purpose of the Study:

• To investigate the role of the HDAC6 ZnF UBP domain in modulating Tau aggregation.
• To explore the direct interaction between HDAC6 ZnF UBP and the Tau protein.

Main Methods:

• Studied the interaction between HDAC6 ZnF UBP domain and Tau protein.
• Assessed the effect of HDAC6 ZnF UBP on Tau self-aggregation and disaggregation.
• Analyzed concentration-dependent effects and conformational changes in Tau.

Main Results:

• HDAC6 ZnF UBP directly interacts with the polyproline/repeat region of Tau.
• This interaction reduces Tau's propensity to aggregate and disaggregates pre-formed Tau aggregates.
• HDAC6 ZnF UBP binding induces conformational changes in Tau and promotes its degradation.

Conclusions:

• The HDAC6 ZnF UBP domain directly modulates Tau aggregation and conformation.
• HDAC6 ZnF UBP may play a role in Tau pathology by reducing aggregation and promoting degradation.
• Findings suggest potential therapeutic implications for neurodegenerative diseases involving Tau.