Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease, characterized by motor neuron death in the brain and the spinal cord. ALS manifests as sporadic (sALS) in most cases (around 90%) or familial (fALS) in around 10% of occurrences, which are related to genetic causes. Previous studies have already related ALS to a variety of factors such as inflammation, excitotoxicity, inclusion of ubiquitinated proteins, autophagy and more specifically mitophagy which has been increasingly more related to the pathogenesis of the disease. On account of that, the objective of our project is to study the relation between autophagy, mitochondrial degradation and cellular survival in a relevant human model for clinical trials composed of induced pluripotent stem cells (IPSCs) of patients with fALS that present the most common mutations such as the ones in SOD1 and C9ORF72. Besides that, we will use modulators of mitochondrial degradation in order to find a possible neuroprotective effect in one or more mutations since there are few therapeutic options that are not very effective to treat the disease. This project is, thusly, relevant not only to better understand how the main mutations related to fALS affect mitochondrial degradation and cellular viability, but also to determine common pathways to the pathogenesis and progression of ALS in the different cell types. Hence, our proposal is extremely relevant to the development of new therapeutic strategies that could inhibit the progression of the disease and promote neuroprotection.
News published in Agência FAPESP Newsletter about the scholarship: