Friends or Foes: Deciphering the details of the role of HtrA proteins in neurodegenerative diseases by NMR spectroscopy.

Alzheimer’s and Parkinson’s disease are the two most wide-spread neurodegenerative diseases severely affecting the daily lives of millions of humans.

The cellular protein quality control system, ensuring a healthy proteome, is an important factor to understand the initial stages of the diseases at the molecular level.

Among these quality control factors are the HtrA proteases (High temperature requirement A), homo-trimeric serine proteases, which are essential regulators in all kingdoms of life.

Despite their importance, details of their involvement in the onset and progression of Alzheimer’s and Parkinson’s remain largely unknown.

I plan to elucidate the functional details of two human HtrA-proteases, HtrA1 and HtrA1, by exploiting advanced high-resolution NMR in solution and the solid-state.

The results of my group will provide completely novel insight into the structural, dynamical, and functional basis of HtrAs interacting with neurodegenerative-disease related proteins, explaining how they exert their reported neuroprotective functions and possible effects on disease progression.

Besides providing groundbreaking novel insights into how the HtrA-proteases are involved in the different stages of the neurodegenerative diseases, our integrated structural biology approach using solution state as well as solid-state NMR spectroscopy in combination with single-particle cryo-EM will provide a strong technical platform for future applications of different types protein complexes.