Cluster Lecture Series: Paul Gleeson

June 14, 2022


Speaker: Paul Gleeson, PhD (Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne)


Date & Time: June 14th, 2022, 01:00 PM

Title: Cell biology of amyloid precursor protein processing and production of amyloid peptides in Alzheimer’s disease



Multiple pathways contribute to the pathology of Alzheimer’s disease (AD), including toxic amyloid b peptides (Aβ), accumulation of insoluble neurofibrillary tangles, and chronic neuroinflammation. It is clear from familial mutations leading to early onset AD (EOAD), and from animal models of AD, that increased amyloid precursor protein (APP) processing resulting in increased levels of Aβ, represents the initial driver of AD that seeds the onset of disease. Our research is aimed to understand the basic cell biology associated with dysfunctional APP processing by the secretases in the endocytic and secretory pathways, critical information to identify new therapeutic targets. We are using a range of biochemical and imaging tools to define the trafficking and itinerary of APP and the b-secretase, BACE1, in various cell systems, including primary neurons. A recent key finding is that APP and the β-secretase, BACE1, are segregated into distinct transport pathways in the secretory pathway, which regulates the level of amyloid β production. I will discuss how the impact of familial AD mutations and perturbations in segregation of APP and BACE1 during Golgi transit, mediated by a variety of different processes, can result in enhanced Aβ production and neurotoxicity. The application of iPSC derived human neurons to the understanding of dysfunctional APP processing and AD will also be discussed.



Host: Janine Becker-Gotot



Online Participation:

On-Site Participation: No Registration needed!