BIO211

Proteostasis, or protein homeostasis, is emerging as the central cellular process controlling the stability, function, and quality control of the proteome. The proteostasis machinery maintains the function of destabilized and mutant proteins, assists the degradation of damaged and aggregated proteins, and monitors the health of the proteome, adjusting it in response to environmental or metabolic stresses. Most mutations linked to disease act by challenging the structure, stability or function of proteins. Thus, understanding and manipulating proteostasis could hold the key for the therapeutic treatment of a wide range of diseases. Cellular proteostasis declines during aging, leading to increased prevalence of late-onset aggregation-linked amyloid diseases implicated in many devastating neurodegenerative diseases (e.g. Alzheimer's, Parkinson's, ALS). We will discuss basic and translational advances of the Proteostasis field and their potential to lead to novel therapies for a wide range of diseases including neurodegeneration, cancer, cardiomyopathy, cystic fibrosis, cataract, metabolic deficiencies and other chronic maladies. Topics to be Covered: 1. Protein Folding and the Molecular Chaperone Concept; 2. Mechanisms and Principle of Molecular Chaperone Action; 3. What is Proteostasis: protein folding and homeostasis in vivo; 4. The Ubiquitin Proteasome pathway and Protein Quality Control; 5. Protein Aggregation, Amyloids and Neurodegenerative Disease; 6. Proteostasis dysfunction and ageing; 7. Therapeutics targeting "proteostasis."