Molecular Chaperones in Neurodegeneration

Abstract

Neurodegenerative diseases are characterized by the degeneration of our brain cells. One of the most common neurodegenerative diseases is Alzheimer’s Disease. The underlying cause of diseases like Alzheimer’s Disease are yet unknown, but what we do know is that the accumulation of proteins plays is crucial role in these pathologies. Proteins are of great importance for the normal wellbeing of our cells but can only do so when properly folded. One can compare it to moving boxes, which are only functional when properly assembled. Misfolded proteins can start to accumulate in the cell, eventually leading to cellular death.

In my thesis I focused on the role of molecular chaperones – who play a supportive role in the folding process of proteins – in neurodegenerative diseases. In several chapters I look at this from a varying point of view. In one chapter for instance, I show that a very specific pathway of molecular chaperones is altered in Alzheimer’s disease, while the working hypothesis for long has been that most chaperones may be depleted in disease.

In other chapters I investigated whether we can tackle very specific parts of the control mechanism in our cells to prevent or degrade the accumulation of misfolded proteins. The development of such intervention strategies will hopefully bring us one step closer in developing new therapeutic strategies for neurodegenerative disease.