Pharmaceutical enhancement of autophagy in an APP/PS1 transgenic mouse model of Alzheimer’s disease.
Macroautophagy, a catabolic process critical for cellular homeostasis, is dysfunctional in Alzheimer’s disease (AD) and associated with neurodegeneration and cognitive impairment. Targeting this process through administration of pharmaceuticals such as the peroxisome proliferator-activated receptor alpha (PPARα) agonist Gemfibrozil may provide a viable alternative to current ineffective therapies for AD.
In my preliminary work, Gemfibrozil was administered sub-chronically to wildtype B6C3 mice and an APP/PS1 transgenic mouse model of AD. Mice treated with Gemfibrozil showed changes in brain protein levels of markers of autophagy. Following these encouraging findings, I completed a long-term study in which wildtype and transgenic mice were administered Gemfibrozil for six months, prior to behavioural, electrophysiological and neuropathological analyses. Long-term treatment with Gemfibrozil was associated with some behavioural improvements in transgenic mice, with associated changes in autophagic markers and reduced neuropathology.
Based on these studies, Gemfibrozil, currently used clinically for hypercholesterolemia and hyperlipidemia, is a viable drug candidate for targeting the dysfunctional autophagy-lysosomal pathway in AD and should be further investigated clinically for repurposing as a therapeutic intervention for AD.
|Date||Tuesday, 29 October 2019|
|Time||12:00pm - 1:00pm|
|Event Category||Health Sciences|
|Location||Biochemistry Seminar Room 231|