The cell autonomous and non-cell autonomous role of TBK1 in disease progression in a mouse model of ALS.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease with no therapies available today. Understanding pathological mechanisms of the disease is the key to identify therapeutic targets. This project seeks to identify how mutations in TBK1, one of the most recent genes associated with ALS, differentially affect the cells of the spinal cord that participate in the pathogenesis of ALS. We will use genetic manipulation of mouse models to test the hypothesis that mutations in TBK1 that cause loss of function of the protein that it encodes for, differentially affect the neurons and the immune cells of the spinal cord. We anticipate that the results from this experiments will broaden the little understanding that we have to date of the role of TBK1 in neurodegenerative disease progression and will set the basis for future work aimed at identifying therapeutic targets for patients with mutations in this gene.