VIB research may lead to effective alzheimer’s therapies

21 January 2017
​Alzheimer’s disease affects more than 48 million people worldwide, eventually leaving them unable to care for themselves. In researching the activation mechanism of the Fyn kinase – a likely cause of Alzheimer’s disease – a team of scientists led by Nico van Nuland (VIB-VUB) and Tom Lenaerts (VUB-ULB) has shed new light onto how this kinase is controlled. Cells use kinases, which are enzymes, to regulate processes like metabolism, signaling and nutrient transport, making them high-potential research targets. Nico and Tom’s research describes how Fyn is regulated, paving the way for a drug with the potential to deactivate it and possibly halt or reverse the effects of Alzheimer’s disease.

Kinases are switched on and off by the cell using a mechanism that disrupts how proteins interact on a molecular level through side chains – chemical groups directly attached to a protein’s backbone that can influence the shape and function of the protein. By examining the specific toggling mechanism that the Fyn enzyme uses to regulate itself, the team gained valuable insight into the role that protein side chains play in the process. Related research has showed that toggling off Fyn in mice with the disease reduces memory problems in these mice.

How Fyn leads to Alzheimer’s disease
The Fyn kinase is switched on through the activities of its side chains, causing it to alter a protein called Tau, eventually leading to the disintegration of crucial elements of brain cells. This new research provides drug developers with in-depth knowledge of the kinase’s regulatory system, possibly leading to medicines that deactivate Fyn in Alzheimer’s patients. This is an important breakthrough, as the only treatments that currently exist for this disease only temporarily improve symptoms and do not address the underlying causes.

Paying tribute to a courageous collaborator and an excellent scientist
The authors of this paper would like to dedicate it to fellow researcher and scientist Nico van Nuland, who was diagnosed with Amyotrophic Lateral Sclerosis (ALS) a few years ago. He has been courageously fighting this disease despite the poor prognosis. Without his expert knowledge, lively support and warm friendship, the team asserts that these results would never have been realized.

Nico, who specializes in protein-protein interaction, is a world-class scientist with very deep experience in nuclear magnetic resonance spectroscopy. His expertise was hugely beneficial to this research, and his many years of intensive work with VIB and numerous collaborators have been an invaluable asset not only to our organization, but to the entire scientific community.

Jo Bury (VIB): “Attracting Nico from Granada to come and work at VIB was a great decision for both sides. Nico brought his tremendous expertise in NMR technology to VIB and set up our NMR centre in no time. His expertise and dedication was amazing. His efforts made it possible to integrate the NMR technology into different sub-disciplines of life sciences. This interdisciplinary approach to studying disease pathways, and the possibility of revealing the dynamics of protein structures of different targets via NMR, have resulted in several scientific breakthroughs and will continue to do so in the future. Nico was always ready to share his expertise with fellow researchers, which makes him a very valued and respected person within the
VIB community.”

Publication
Huculeci et al., Structure 2016


Nico van Nuland (VIB-VUB)