Small molecule screening for HtrA2 activation to mitigate neurodegenerative diseases
This research focuses on screening small molecule compounds to activate HtrA2, a mitochondrial protease, potentially restoring mitochondrial function and mitigating neurodegenerative diseases by blocking the PDZ domain.
Overview
This innovative research initiative seeks to identify and screen small molecule compounds that can activate HtrA2, a mitochondrial serine protease crucial for maintaining proteostasis and mitochondrial quality. By targeting the C-terminal flap-like PDZ domain, the aim is to restore HtrA2 functionality, which may aid in cell survival and combat neurodegenerative diseases linked to mitochondrial dysfunction, such as Parkinson's and Alzheimer's diseases.
Technical specifications
HtrA2 is essential for mitochondrial health, as its reduced activity is linked to numerous diseases due to the accumulation of unfolded proteins and reactive oxygen species. The research involves:
- Bioinformatic docking: Designing chemical ligands that bind to the PDZ domain of HtrA2 using the resolved protein structure.
- Compound identification: Importing potential structures into Molport to find purchasable compounds with similar structures.
- Screening assays: Utilizing up to 50 shortlisted compounds to measure mitochondrial respiration, reactive oxygen species, and cytokine profiles using assays like the Seahorse mitochondrial stress test and immunoblotting.
Technology readiness level
This research is currently at Technology Readiness Level 3, indicating that the concept and its components are undergoing active research and validation screening in a laboratory setting.
About University of Tübingen
Eberhard Karls University of Tübingen is a large, comprehensive public research university in Baden‑Württemberg with a global outlook and a strong record of basic and translational discovery. Its integration with a major university hospital supports clinical research and translation at scale. Co‑located national research institutes and a vibrant regional innovation ecosystem enable joint labs, shared facilities, and industry‑sponsored collaborations, while proximity to Stuttgart’s manufacturing and mobility hub facilitates pilot testing and scale‑up. Research is supported by competitive funding from the German Research Foundation, the Federal Ministry of Education and Research, and European Union programs. A dedicated technology transfer office manages IP, licensing, startup formation, and streamlined contracting for corporate R&D.
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