Alzheimer’s Disease is the most common form of dementia and is currently untreatable. When analysing brains affected by Alzheimer, we can notice they have abnormal chunks of matter accumulating in the brain. This matter is mostly composed of proteins. Aggregates of the protein Tau are good predictors of dementia, meaning that their presence can tell us that the brain is sick. Currently, the process of formation of Tau aggregates is thought to be irreversible.
In my thesis, we show that the molecular chaperone Hsp70 – another protein very abundant in neurons - can disassemble Tau fibrils, cutting them into smaller pieces. These findings can have implications for the development of new therapies against Alzheimer: can we boost therapeutically Hsp70 to treat dementia? Why do neurons have such an abundant fibril-cutter, yet they still form Tau aggregates?
The second major finding of my thesis relates to how Tau aggregates behave in the brain, meaning how they interact with other components that make the neuron function. We found that Tau aggregates can attract specific proteins of the brain, and we found a major chemical principle governing such attractions. Can we use the biochemical knowledge we obtained at our own advantage, for instance by blocking such abnormal interactions? This chemical principle is called pi-stacking and it is also used by normal, functional neurons. Are Tau aggregates sabotaging normal neuronal functions using the same chemical principles that make a neuron work?
Answering these questions will get us closer to treat Alzheimer’s Disease.