The University of Queensland

NHMRC-ARC Dementia Fellowship (Australian Based) - Towards targeting the endsome in neurodegenerative disease (2016–2018)

Abstract:

This work falls clearly within the Priority Framework for Dementia Research, covering research into both the Origins and Mechanisms of dementia and related neurodegenerative diseases. Disruption of the SNX27-retromer protein complex is strongly linked to Parkinson¿s disease (PD) and Alzheimer¿s disease (AD). Furthermore, a small molecule `chaperone¿ that stabilizes and enhances SNX27-retromer function can alleviate cellular accumulation of toxic proteins that cause these diseases, suggesting a novel pathway to therapeutic intervention. A molecular understanding of this AD and PD-related protein complex is now urgently needed, and this proposal will define the structural basis of how the SNX27-retromer complex governs the intracellular trafficking of receptors and enzymes that play critical roles in these diseases. The proposed work will provide new insights into the molecular basis of PD and AD, and establishing a foundation for the future design of targeted therapeutics. I therefore propose to work alongside Dr. Brett Collins who has made seminal contributions involving the functions of peripheral membrane proteins including retromer and sorting nexins in endosomal sorting.

Grant type:

NHMRC-ARC Dementia Research Development Fellowships Scheme

Funded by:

National Health and Medical Research Council