Activity-Based Probes for the High Temperature Requirement A Serine Proteases

Area of Science:

• Biochemistry
• Molecular Biology
• Neuroscience

Background:

• High temperature requirement A (HTRA) serine proteases are crucial for protein quality control.
• Dysregulation of HTRA proteases is implicated in neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD).
• Understanding HTRA activity regulation is limited by the lack of specific chemical probes.

Purpose of the Study:

• To develop novel activity-based probes (ABPs) for monitoring HTRA protease activity in live cells.
• To investigate the role of HTRA proteases in neurodegenerative disease models.

Main Methods:

• Synthesis of novel activity-based probes (ABPs) targeting HTRA proteases.
• Application of ABPs in live cell imaging and activity quantification.
• Utilizing a mitochondrion-targeted probe to observe HTRA2 activity.

Main Results:

• Demonstrated the utility of novel ABPs for monitoring HTRA activity in live cells.
• Observed significantly elevated HTRA1 activity in an AD-like cell model.
• Successfully visualized active HTRA2 within mitochondria in live cells.

Conclusions:

• Developed effective chemical probes for studying HTRA protease activity.
• The probes provide a valuable tool for investigating HTRA roles in neurodegenerative diseases.
• HTRA1 activity is notably increased in an Alzheimer's disease cellular model.