What are the Best Drug Targets for Alzheimer’s Disease?

Alzheimer’s Disease is one of the leading causes of death and its importance is increasing with our ageing population. There is no cure. Early onset AD, that is diagnosed before the age of 65, is usually caused by a dominant mutation in the presenilin enzyme which leads to an increase in production of the A42 peptide. Aggregation of A42 in the brain initiates a cascade of processes, including protein phosphorylation, oxidative stress and inflammation, ultimately causing neuronal damage and death.

Recent breakthroughs in stem cell technology now allow us to turn fibroblast skin cells taken from AD patients into other cell types. For example, we have cells with a presenilin mutation from a patient who died at 51 from early onset AD that we can differentiate into neurons and other types of brain cell. These cells are excellent models for AD, showing various phenotypes, such as changes in shape and growth, mitochondrial dysfunction, oxidative stress, loss of synaptic function and inflammation.

Potential AD drugs may work interfere with various steps in the amyloid cascade, such as inhibiting presenilins and other enzymes involved in A42 production, preventing A42 aggregation, and reducing oxidation or inflammation. Which of these strategies would be best is unclear. Ideally a drug should reverse all these detrimental phenotypes.

In this project, we will test a range of model drug compounds that inhibit key potential targets for AD. The effects of the drugs will be measured in our AD model neurons to see whether they are effective at reversing the AD phenotypes and compared to healthy neuronal cells as controls. For example, we will find out whether inhibiting A42 aggregation is able to reduce inflammation or restore mitochondrial function.

At the end of this project, we will have found which are the best targets for AD and how different drug types affect neurons. This will guide future drug development for this very important disease. The student will learn how to grow, differentiate and characterise cells using a wide range of methods, providing an excellent training in cell biology and neuroscience.

Qualification
Applicants should have or expect a good II(i) honours degree (or an equivalent degree) in Biology, Biochemistry, Chemistry or a related subject.

Contacts for further information
For enquiries about admission, qualifications etc. please email [Email Address Removed].

For enquiries about the project please email [Email Address Removed].