National Institute on Aging 1RF1AG098171-01A1

Role of ferroptosis of oligodendrocytes and vascular endothelial cells in vascular and Alzheimer's Disease related dementia

The award funds research on the role of ferroptosis in vascular and Alzheimer's disease-related dementia, focusing on mechanisms of white matter injury and potential therapeutic targets involving hyaluronan metabolism.

Description

This proposal focuses on mechanisms related to vascular dementia involving ferroptosis, a form of cell death affecting blood vessels and oligodendrocytes, which generate myelin. The study employs human cases and mouse models to understand how ferroptosis disrupts blood flow and contributes to white matter injury, aiming to identify potential therapies. Progress in understanding white matter injury (WMI) in vascular cognitive impairment and dementia (VCID) is limited by gaps in knowledge about glial mechanisms of remyelination failure. The project investigates the role of hyaluronan (HA) and its digestion by CEMIP hyaluronidase in WMI, focusing on ferroptosis in vascular endothelial cells and oligodendrocyte lineage cells. It explores how HA metabolism influences cell survival and how VCID and Alzheimer's Disease (AD) interact to accelerate WMI, with the goal of developing strategies to block HA metabolism as potential treatments.

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