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ELUCIDATING AN INHIBITORY ROLE OF MAP2 IN TAU FIBRILLIZATION

Award Number: R21AG060229
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2018
PERIOD OF PERFORMANCE END DATE: 04/30/2021

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ELUCIDATING AN INHIBITORY ROLE OF MAP2 IN TAU FIBRILLIZATION - Currently, there are no drugs that halt the progression of Alzheimer's disease (AD). This constitutes an important problem because >5 million people in the United Sates are affected. The deposition of Tau fibrils throughout the brain is a pathological hallmark of the disease. Targeting the fibrils holds promise for therapeutic intervention. MAP2 is a protein that is highly homologous to Tau and is found in close proximity to Tau deposits. The objective of this proposal is to determine how MAP2 modulates Tau fibril formation. The central hypothesis is that MAP2 caps Tau fibrils at the ends and thereby inhibits fibril growth. This hypothesis has been formulated based on data produced in the applicant's laboratory that reveals specific interactions between Tau fibrils and MAP2. The rationale is that once the modulatory roles of MAP2 are resolved, new strategies can be developed that utilize MAP2 as a blocking agent of Tau fibril formation. Supported by strong preliminary data the central hypothesis will be tested by pursuit of the following three specific aims. 1) Evaluate the inhibitory effects of MAP2 on the elongation of AD-derived Tau fibrils. 2) Identify the molecular mechanism of MAP2-mediated inhibition. 3) Determine how MAP2 modulates the propagation of distinct Tau fibril conformers. The research is innovative because it establishes an endogeneous protein with high sequence homology to Tau as a potent new inhibitor of Tau fibrillization. The proposed research is significant because it is expected to lead to new strategies for the prevention and treatment of a wide range of Tau misfolding diseases including AD. The research is exploratory and lays the foundation for future studies into the phenotypic diversity of human Tauopathies and novel therapeutic approaches that utilize homology-based inhibition of Tau fibrillization.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = -$250 )
2021	2019	COLORADO SEMINARY	2199 S UNIVERSITY BLVD	DENVER	CO	80210	DENVER	USA	Aging Research	000	2	8/20/2021	NON-COMPETING CONTINUATION	-$250
														Subtotal = -$250

Issue Date FY: 2019 ( Subtotal = $184,627 )
2019	2019	COLORADO SEMINARY	2199 S UNIVERSITY BLVD	DENVER	CO	80210	DENVER	USA	Aging Research	000	2	4/8/2019	NON-COMPETING CONTINUATION	$184,627
														Subtotal = $184,627

Issue Date FY: 2018 ( Subtotal = $219,260 )
2018	2018	COLORADO SEMINARY	2199 S UNIVERSITY BLVD	DENVER	CO	80210	DENVER	USA	Aging Research	000	1	8/14/2018	NEW	$219,260
														Subtotal = $219,260

Grand Total All Awards = $403,637

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ELUCIDATING AN INHIBITORY ROLE OF MAP2 IN TAU FIBRILLIZATION

Award Number: R21AG060229

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/15/2018

PERIOD OF PERFORMANCE END DATE: 04/30/2021

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