Molecular dissection of the enzyme responsible for amyloid-beta protein production in Alzheimer's disease
With increasing incidence of Alzheimer’s disease (AD) and a lack of disease modifying treatments, a rational approach to developing therapeutics is critical. One example is targeting the enzyme that directly generates the amyloid-beta protein (Aβ). The build-up of Aβ in the AD brain occurs early in the disease process. Trials to date, targeting the gamma-secretase (“g-sec”) enzyme have been associated with severe side effects. More selective targeting is required if this enzyme is to be pursued as a therapeutic. During Melissa's honours year, she identified the combination of areas within one component of “g-sec”, the presenilins, involved in Aβ production. I this PhD project, Melissa will use both laboratory experiments and computer modelling to now validate, refine and pinpoint area(s) within presenilins critical for Aβ production. This work will ultimately offer potential targets for designing more selective small molecule therapeutics aimed at slowing down or preventing build-up of pathogenic Aβ.
Melissa Eccles commenced her PhD in 2018 at the Curtin Health Innovation Research Institute at Curtin University, Western Australia.