Molecular mechanisms that underlie corticospinal motor neuron vulnerability and degeneration in ALS

This proposal has great relevance to ALS and has a unique importance, as it involves the use of upper motor neurons in an effort to expand our understanding for the selective motor neuron vulnerability both in the cortex and the spinal cord. There has been great advances in our understanding on the cellular mechanisms that lead to spinal motor neuron degeneration, but the factors that are involved in upper motor neuron vulnerability remains mainly unknown. However ALS, different from other motor neuron diseases, is characterized by the progressive degeneration of both the cortical and spinal motor neurons. Therefore, mechanisms that are involved in upper motor neuron degeneration must be studied together with spinal motor neurons. Ozdinler Laboratory has generated tools and approaches in an effort to shed light onto the upper motor biology in ALS. Upon completion of this proposal, we will have an understanding of the molecular and genetic mechanisms that are selectively upregulated and downregulated in vulnerable motor neurons. Our findings will reveal the canonical pathways that are selectively activated/inactivated and will point to the presence of potential early detection markers in ALS. This is very relevant to ALS and it is crucial for developing effective treatment strategies.