Cellular and Molecular Mechanisms of Prion-Like Aggregate Seeding, Propagation, and Neurotoxicity in AD/ADRD (R01 Clinical Trial Not Allowed)

US Dept. of Health & Human Services: National Institutes of Health (NIH)

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Deadline: Oct 24, 2022 (Full proposal)

Grant amount: Up to US $500,000

Fields of work: Neuroscience Neurological Diseases & Disorders

Applicant type: Government Entity, Indigenous Group, Nonprofit, For-Profit Business

Funding uses: Research

Location of project: Preferred: United States Other eligible locations: Anywhere in the world

Location of residency: Preferred: United States Other eligible locations: Anywhere in the world

Overview:

The accumulation of misfolded proteins in the brain is a key pathological feature shared by many neurodegenerative diseases that can result in dementia such as Alzheimers Disease, Lewy Body Diseases, Frontotemporal Degeneration, and cerebral amyloid angiopathy. Classical prion diseases such as Creutzfeldt-Jakob Disease are a rare family of neurodegenerative disorders that occur when the cellular prion protein (PrPC) undergoes structural conversion to a pathological form (PrPSc), which is usually triggered by its interaction with an infectious variant of the protein that forces the conformational change. Once this process is initiated, it becomes self-propagating until toxic aggregates accumulate within the CNS, leading to neuronal death. Because misfolded proteins of AD/ADRD have been reported to share some features with pathological prion protein at the structural level, it has thus been proposed that ADRD-relevant proteins such as Alpha, tau, beta-synuclein, and TDP-43 (among others) may exhibit prion-like behaviors that lead to toxic aggregate and tangle formation. The goal of this initiative is to promote studies that increase our understanding of the cellular and molecular mechanisms by which such prion-like conversion events occur and are propagated in AD/ADRD, as well as the downstream mechanisms that trigger neurotoxicity, pathological and circuit changes in the brain.

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This page was last reviewed July 26, 2022 and last updated July 26, 2022