ºÚÁÏÉç

​​Successful disease-modifying treatments remain an unmet clinical need for Alzheimer’s Disease (AD). 

Alzheimer’s pathology is multi-factorial and includes:

• neurodegeneration
• cholinergic dysfunction
• formation of amyloid plaques
• the hyperphosphorylation of Tau protein
• inflammation. 

To address the need to develop a multifunctional approach we will identify and characterize hydrogen sulfide (H2S) compounds derived from Brassica species (e.g. broccoli, cabbage) on the rationale that:

•  H2S confers neuroprotection by preventing aggregation of  Î²-amyloid,  a key early event in AD development
• the compounds will act as a cholinesterase inhibitor
• H2S sulfhydrates glycogen synthase kinase-3β (GSK3β) to inhibit its activity, thereby preventing hyperphosphorylation of Tau, a key late event in the pathogenesis of AD
• H2S acts as a potent anti-inflammatory, anti-oxidant and antimicrobial agent

Inflammation, oxidative stress and microbial activity have recently been cited as major trigger events in the development of AD. There is also good recognition that preventive or lifestyle approaches, including diet and nutrition, have potential as both pre-emptive and disease modifying conditions. Identifying and investigating the mechanistic basis for these approaches is an important unmet need. 

To deliver our aims, the student will utilize a combination of in-vitro human cell lines, a preclinical C. elegans model organism and human brain organoids to test plant-derived multi-functional compounds for the treatment of AD.​ 

Supervisors

In addition to being supervised by Professor Jessica Teeling (lead supervisor), Professor Vincent O'Connor, and Professor Mark Chapman from the ºÚÁÏÉç, you will also be supervised by from the Wageningen University and Research and from the Royal Botanic Gardens, Kew.