Investigating the causes of neurodegenerative diseases

We are living longer and longer and therefore more and more people are affected by neurodegenerative diseases. This year's William Chalmers honorary lecture was given by Professor Pernilla Wittung-Stafshede who has dedicated her career to finding the answers to how brains become ill – and she has already come a long way towards better understanding. ​
Pernilla Wittung-Stafshede first started to be interested in how key molecules in the body work when she herself was a doctoral student at Chalmers. While doing her postdoc in the USA, she began to investigate how proteins in the body fold to globular shapes in order to function. During the last decade she has become interested in ‘bad’ proteins, probing the reasons they fold incorrectly, start to ‘clump’ together, and thereby cause diseases. 
 “I want to understand, at the molecular level, why proteins become prone to fold incorrectly, which clumps of misfolded proteins are dangerous, and how this kills cells. If we know this, we could be able to prevent and cure illnesses like Alzheimer’s, Parkinson’s, and ALS,” she says. 

The answer could lie in the gut
Some of her discoveries connect to gut bacteria and what food we eat. For example, there is a protein common in fish that was found able to absorb and remove the wrongly-folded protein causing Parkinson, but so far only in the test tube.
 “We have also observed that in a mice model of Parkinson’s, mice with normal bacteria in the gut get Parkinson’s, but mice without gut germs are protected. This is a clear sign that Parkinson’s, and maybe even other neurodegenerative diseases, might actually start in the stomach and be influenced by what we eat. There is a lot to investigate here – not least when you consider that there are more bacteria in the gut than there are cells in our entire body!” she explains. 

Metals play a role
Early in her career, Pernilla Wittung-Stafshede laid the foundation for a new research direction – by looking at how metal-binding proteins fold and what specific role the metal played in the folding process. Nobody had looked at this before although almost half of our proteins bind a metal ion, and she made several ground-breaking discoveries. Furthermore, she was one of the first to start to mimic the crowded cellular environment in her test tube experiments, and it was found that this crowding effect was an important factor for protein properties. Pernilla’s combined interests in metals and misfolding of proteins may provide synergy in her future research, because metal levels in the brain are often disturbed in neurodegenerative disorders. For example, the level of copper is low in the brains of Alzheimer’s and Parkinson’s sufferers.
 “Those who suffer from neurodegenerative diseases often have too little copper in their brains, and they could potentially benefit from copper supplementation,” she says. "However, this is controversial as copper may also be toxic."

Current medicines don’t address the problem directly
Both a genuine curiosity and a desire to find cures for neurodegenerative diseases are what drive Pernilla Wittung-Stafshede to look further into protein misfolding mechanisms. For only with basic knowledge, will be able to develop a cure, or, even better, prevent the illnesses in the future. Today’s medicines do not attack the root of the problem, rather they simply improve neurological pathways short term.
“My dream is to find something which offers a general solution to all protein-misfolding diseases” she says. 

At this year’s popular-science William Chalmers Lecture, Pernilla Wittung-Stafshede spoke about her research, at the same time as we at Chalmers celebrated our birthday, on the 5th of November. We invited the public for cake and bubbles.  

The lecture was also broadcasted (in Swedish) on Chalmer's social channels

Text: Helena Österling af Wåhlberg
Photograph: Oscar Mattsson​

Pernilla Wittung-Stafshede…
…has been professor at the Department for Biology and Biotechnology and Head of the Division for Chemical Biology, since 2015. She leads a research group which focuses on metal-binding proteins and protein misfolding. Previously, she worked as professor at the universities of Rice and Tulane in the USA, as well as at Umeå university. She has published over 220 research articles.

Published: Thu 11 Oct 2018. Modified: Fri 16 Nov 2018