Autophagy and neurodegeneration

Published on October 31, 2018   39 min
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I'm David Rubinsztein from the Cambridge Institute for Medical Research. Today, I will give an overview of the links between autophagy and neurodegeneration. While these will be primarily illustrated with examples from my lab, I want to stress that many others have made important contributions to this area.
I'm going to structure my talk in three components. First, I will give an overview of some older work that describes key relationships between autophagy and neurodegeneration. I'm then going to move on to more recent studies illustrating how we searched for new signals that regulate the autophagy process, and in the third part of the talk, I'm going to focus on trying to understand how the process of autophagy might be compromised in various neurodegenerative diseases.
Most of the neurodegenerative diseases that afflict man manifest with the intracellular accumulation of aggregate-prone proteins in inclusions. So, on this slide, you can see in boxes A and D panels from Huntington's disease brains showing such inclusions. B and E show Parkinson's, and tau in Alzheimer's disease in E, and C and F show extracellular inclusions in Alzheimer's disease. Today we're primarily concerned with the inclusions that form within the cells in the cytoplasm. In these cases, for instance in Huntington's disease and Parkinson's disease and tau, there is extensive genetic and transgenic data arguing that these proteins are toxic for the cells and manifest toxicity by gain-of-function mechanisms. Therefore, a key objective we've had in my lab for many years, is to see if we can enhance the clearance of such mutant proteins relative to their wild-type counterparts.