Project - Targeting protein aggregation for the treatment of neurodegenerative diseases

Disease area:

AD, FTD, ALS

Research Project Description

Dementia encompasses a wide range of neurodegenerative diseases such as Alzheimer’s disease, frontotemporal dementia and amyotrophic lateral sclerosis. Dementia related diseases currently affect more than 50 million people worldwide. Without a major medical breakthrough, the number of patients suffering from these diseases is estimated to more than double by 2050. The treatment of these neurodegenerative diseases represents one of the major frontiers in modern medicine as current therapeutic options for patients are limited. The current treatment options (or lack thereof) and the global scale associated with these disease states suggests that research in this field is crucial. A key pathological symptom of many neurodegenerative disease states is the formation of insoluble protein aggregates. Insoluble protein aggregates mediate cellular malfunction and ultimately lead to cell death and subsequent neurodegeneration. Aggregation of the microtubule associated protein Tau and the transactive response DNA binding protein TDP-43 has been heavily implicated in a number of dementia disease states, particularly Alzheimer’s disease and frontotemporal dementia. A range of molecular structures have been reported to interact with protein aggregates in various neurodegenerative disease states, however in most cases exploration of the structure-activity relationships and the scope of protein aggregate interactions is limited. Utilising a wide range of techniques including in vitro and in silico studies this project focuses on the design, synthesis and biological evaluation of a range of drug-like compounds as inhibitors of Tau and TDP-43 aggregation for treatment of neurodegenerative disease states.