Danish researchers reveal key receptor implicated in Alzheimer’s disease
Their finding may lead to the development of a novel drug to treat this dreaded dementia disorder.
Researchers regularly discover rare genetic variants when studying a disease – without being able to say whether, or how, the specific variant is actually implicated in the disorder in question.
This receptor helps regulate the so-called glial cells responsible for the brain’s immune response
It is frustrating, but it also poses a challenge.
If we could understand the genetics, perhaps we could come up with good ideas for new drugs to treat the disease.
Researchers studying Alzheimer’s disease have found themselves in this exact situation for many years now regarding the Siglec-3 receptor.
‘This receptor helps regulate the so-called glial cells responsible for the brain’s immune response,’ explains Professor Henrik Clausen, head of the Copenhagen Center For Glycomics (CCG) at the University of Copenhagen.
And as Christian Büll, a postdoc at CCG, says, we know that certain mutations of Siglec-3 are often associated with a hereditary version of Alzheimer’s typically found in younger patients: ‘But until recently, we didn’t understand the link and how the Siglec-3 receptor is actually regulated. We now bring new knowledge to the table.’
Christian Büll is the lead author of an article recently published by CCG researchers in the scientific journal PNAS.
The article demonstrates how, in collaboration with colleagues from the Netherlands and the USA, the Danish researchers were the first to successfully decipher Siglec-3.
‘And we can use the knowledge we now have to try to design a drug to prevent certain mutations in the Siglec-3 receptor from contributing to the development of Alzheimer’s disease. This step is not just round the corner, but it makes sense to continue on this path,’ says Associate Professor Yoshiki Narimatsu, who headed the study with Professor Clausen and is one of the other researchers behind the article.
A sugar library
There are a variety of sugars on the surface of the body’s – and the brain’s – cells in humans and other mammals. This “sugar coating”, which varies in composition from cell type to cell type, has a number of roles.
Among other things, the complex coating of sugars helps regulate the immune cells whose job it is to combat disease.
The many different sugars on the surface of our cells also play a role in disease. For example, they have implications for the way in which cancer cells spread.
What’s more, the coating can act like Velcro hooks, allowing viruses and infectious bacteria to identify the cells they wish to bind to and attack.
When it comes to understanding disease as well as developing new therapies and drugs, it is therefore extremely important to know which bacteria, viruses, and immunity-regulating receptors bind to which cells and sugars.
Acquiring these data requires extensive biochemical investigation, and this is only possible with the help of a special technology developed by the CCG researchers with funding from the Lundbeck Foundation.
This special technology is an entire library of genetically engineered, human cells which act as a kind of “sugar detective”. For example, the method can reveal how Siglec-3 is regulated by specific sugars found on the surface of brain cells.
‘But this library, which we are constantly extending, can also be used to generate good ideas for many conditions other than Alzheimer’s disease, such as autoimmune disorders and cancer,’ says Professor Clausen.