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Role of ryanodine receptors in Alzheimer’s disease

Year:
2020
Duration:
36 months
Approved budget:
$1,189,936.70
Researchers:
Associate Professor Peter Jones
,
Dr Laura Gumy
,
Dr Shane Ohline
,
Professor Ruth Empson
,
Professor Cliff Abraham
,
Professor William Louch
Health issue:
Neurological (CNS)
Proposal type:
Project
Lay summary
Alzheimer’s disease (AD) affects ~10% of people aged 65 and older, positioning it as a major concern for New Zealand’s aging population. Current treatment options for AD are limited due to an incomplete understanding of the molecular changes occurring within nerve cells during AD. However, a growing body of evidence shows that inappropriate leak of Ca2+ within nerve cells, through a protein channel (RyR2), is associated with AD, and that prevention of this leak may protect against the disease. However, why this leak occurs is poorly understood. Within the heart, we and others have shown that Ca2+-leak can be caused by the inappropriate localisation of RyR2 within the cell. This project will determine if a similar mechanism underlies Ca2+ dysfunction in AD neurons. It will additionally examine whether clinically relevant drugs known to prevent Ca2+-leak in the heart also work in neurons, and consequently may represent new treatments for AD.