Fuz protein and neurological disorders

18 August 2018

Professor Edwin Chan is one of the very few scientists working on rare neurodegenerative diseases. His recent research revealed the pathogenic mechanism for a group of rare genetic neuronal disorders known as polyQ diseases.

Proteins need to adopt proper functional shapes before they can carry out their duties in cells. Any improper folding of a protein may result in cellular malfunctioning and lead to diseases. In polyQ diseases, misfolded disease proteins are detected in the deteriorating neurons of polyQ disease patients.

Professor Edwin Chan (Croucher Scholarship 1996) showed that the polyQ protein aggregates perturb the function of Yin Yang 1 protein. In neurons, Yin Yang 1 protein functions as a repressor of Fuz protein. When the function of Yin Yang 1 is compromised, the expression level of Fuz will increase. Once Fuz level reaches 2.5 times of the normal level, it will trigger apoptosis and cause cell death in neurons. Abnormal induction of Fuz expression is commonly found in polyQ patients, proving that this is a pathogenic mechanism of the diseases.

“In the past, scientists only considered Fuz as a player in neurodevelopment,” said Chan.

It is also observed that in Alzheimer’s, the expression level of Fuz also increased. This implies that the Fuz-mediated apoptosis pathway plays some common roles in neurological disorders in general.

Chan is now investigating the involvement of Fuz in other disease conditions, and finding compounds that can bring Fuz upregulation back down to a normal level. His work has been published in EMBO Reports

Aside from understanding rare diseases, Chan is also a staunch advocate for patients of rare diseases. He has appeared in many radio shows and media outlets to share his knowledge and to educate the public. Chan’s research on rare diseases also sparked discussions among policy-makers of the Hong Kong government. 

"I hope to demonstrate how rare disease research can make contributions to the advancement of biomedical science research in neural disease biology,” said Chan. 

Professor Edwin Chan is the Director of the Master of Science Degree Programme in Biochemical and Biomedical Sciences in the School of Life Sciences at CUHK. After completing his bachelor’s degree in biochemistry, he went to the University of Cambridge to take a PhD in genetics. He then received his post-doctoral training in biomedicine at the University of Pennsylvania.

To view Professor Chan's Croucher profile, please click here