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Exploring chaperone code control of TDP-43 function in ALS

Award Number: R21NS133682
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Exploring chaperone code control of TDP-43 function in ALS - Aggregation of the TAR DNA-binding protein (TDP-43) is associated with neurodegenerative disorders such as frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS). Any strategy that alters TDP-43 aggregation, function and cellular toxicity may form the basis of potent novel ALS therapies. A major regulator of protein folding and aggregation in cells is the Hsp70 molecular chaperone. Research has primarily focused on how Hsp70 function specificity arises through regulation of a) expression of Hsp70, b) isoform differences in the Hsp70 protein family and c) the variety of co-chaperone proteins that bind to the Hsp70 molecule. Despite the proteomic identification of over seventy phosphorylation sites on both yeast and mammalian Hsp70, the biological function of most of these sites remains unknown. In this proposal, we intend to investigate the connection between post-translational modification (PTM) of Hsp70 and TDP-43 function. In particular, we will determine how chaperone PTMs are altered in response to the presence of TDP-43 in mammalian and yeast cells and how the modification of these PTMs impacts TDP-43 toxicity. Finally, we intend to use cross-linking mass spectrometry to analyze the interaction between Hsp70 and TDP-43 with a focus on the interaction surface between these two proteins. This information will provide ket preliminary data for larger studies that determine the mechanisms regulating these PTMs and their specific effect on TDP-43.


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: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/4/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $413,826 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/6/2023	NEW	$413,826
														Subtotal = $413,826

Grand Total All Awards = $413,826

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Exploring chaperone code control of TDP-43 function in ALS

Award Number: R21NS133682

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/15/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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