Neurons become vulnerable when they fail to maintain cellular homeostasis, which require very complex dynamics of protein-protein interactions. We think that understanding neuronal vulnerability requires investigation of protein landscape of neurons that begin to show signs of degeneration at a cellular level. Previously, it was impossible to investigate the protein content of distinct neuron populations because they are very limited in numbers and the proteomics approaches were not sensitive enough to detect low levels of proteins. However, we are now at the crossroads of important discoveries. Today we can: 1) isolate pure populations of both healthy and diseased upper motor neurons at different stages of disease; 2) determine the protein content within these pure neuron populations with high precision using top down proteomics approach; 3) determine protein-protein interactions that are critically important for neuron function; 4) using well-defined model systems we can test hypothesis. These novel developments overcome many limitations in the field and allow us to reveal changing protein dynamics in vulnerable and degenerating neurons. This information could identify novel early detection markers especially for diseases in which upper motor neurons are primarily affected, and it could identify novel cellular pathways that are responsible for motor neuron death.
|Effective start/end date||8/1/15 → 7/31/18|
- ALS Association (16-IIP-276)