Non-cell Autonomous Mechanisms: SOD1 Pathology

This lecture covers the mechanisms of motor neuron diseases, focusing on Amyotrophic Lateral Sclerosis (ALS) with an emphasis on the role of mutated SOD1. It discusses the clinical presentation, molecular pathology, and non-cell autonomous mechanisms involved in ALS. The lecture explores the toxic gain of function caused by SOD1 mutations, the cellular toxicity induced by mutated SOD1, and the experimental models used to study ALS in the lab. It delves into the aberrant redox chemistry, protein misfolding, and aggregation of SOD1, as well as the link between ER stress and neuronal hyperexcitability. Furthermore, it addresses mitochondrial dysfunction, excitotoxicity, and the role of glial cells in ALS pathology.