Alzheimer's Disease Supplement to NS070899 Linking Polyglucosans to AD

Grants and Contracts Details

Description

This is an Administrative Supplement request in response to NOT-AG-18-008 for “Alzheimer's Disease and its related Dementias (AD/ADRD)-focused Administrative supplements for NIH grants that are not focused on Alzheimer's disease” for R01NS07899 entitled “Regulation, signaling, and dynamics of glucan phosphatases.” The requested funds are to perform experiments proposed within the scope of R01NS07899, but were not originally focused on Alzheimer’s disease. The parent grant focuses on defining the molecular mechanism of Lafora disease (LD). LD is a fatal, neurodegenerative glycogen storage disease. The pathogenic agent and a hallmark of LD are aberrant, glycogen-like intracellular polyglucosan body (PGB) inclusions. In the parent grant, we propose to: 1) define these PGBs in terms of their physiochemical make-up, 2) define the metabolic machinery that generates them, and 3) develop putative therapeutics to remove them. Recent work has identified PGBs in Alzheimer’s disease patient samples and we see that these PGBs are localized in similar regions as tau. In this supplement, we will utilize our extensive expertise with PGBs: Aim 1: Establish the physiochemical properties of PGBs in Alzheimer’s disease models. Aim 2: Define central carbon metabolism using steady state metabolomics in Alzheimer’s models. Aim 3: Identify and develop an amylase to degrade Alzheimer’s disease PGBs as a putative therapeutic.
StatusFinished
Effective start/end date8/1/184/30/20

Funding

  • National Institute of Neurological Disorders & Stroke

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