Autophagy and Neurodegeneration
Tuesday, November 20th, 2018 - 9 am CST / 3pm GMT / 4pm CET
Intracellular protein aggregation is a feature of many late-onset neurodegenerative diseases, including Parkinson’s disease, tauopathies, and polyglutamine expansion diseases (like Huntington’s disease (HD)). Many of these mutant proteins, like that causing HD, cause disease via toxic gain-of-function mechanisms. Therefore, the factors regulating their clearance are crucial for understanding disease pathogenesis and for developing rational therapeutic strategies.
The two major intracellular protein degradation pathways are the ubiquitin-proteasome system and (macro)autophagy. We showed that the autophagy inducer, rapamycin, reduced the levels of mutant huntingtin and attenuated its toxicity in cells, and in Drosophila and mouse HD models. We have extended the range of intracellular proteinopathy substrates that are cleared by autophagy to other related neurodegenerative diseases including Parkinson’s disease. Autophagy induction is generally considered neuroprotective in various neurodegenerative models, and certain genetic variants in neurodegenerative diseases are associated with compromised autophagy.
- Understand the basic biology of autophagy and its role in neurodegeneration
Understand how genetic variants in Parkinson’s disease, Alzheimer’s disease and polyglutamine diseases impact autophagosome biogenesis.