Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Investigation of the role of ATXN1 in oligodendroglia and neurodegenerative diseases

Award Number: R01AG076154
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

Group Awards By:

View Award Description

Investigation of the role of ATXN1 in oligodendroglia and neurodegenerative diseases - Genetic mutations in ATXN1, which encodes ataxin-1 protein, have been implicated in several distinct neurodegenerative diseases. In humans, wild-type ATXN1 alleles normally contain between 4-36 consecutive CAG codons in the polyglutamine tract of the first coding exon, with those containing greater than 21 repeats typically also carrying 1 to 3 interrupting CAT codons. The expansion of the repeat tract of one ATXN1 allele to 39 or more uninterrupted repeats results in the highly penetrant, late-onset, and progressive cerebellar ataxia called spinocerebellar ataxia type 1 (SCA1). Interestingly, intermediate length expansions of ATXN1 are associated with an increased risk for developing sporadic amyotrophic lateral sclerosis and a form of frontotemporal dementia (FTD) called progressive nonfluent aphasia (PNFA), while intronic mutations that decrease ATXN1 levels also increase risk for Alzheimer’s disease (AD) and multiple sclerosis. Although ATXN1 is ubiquitously expressed in many different cell types throughout the central nervous system, most studies have primarily focused on the role of mutant ataxin-1 in the cerebellar Purkinje cells (PCs), the most obvious population of neurons to degenerate in SCA1. Therefore, the functions of ataxin-1 and the effects of different ataxin-1 mutations in other populations beyond PCs are not well-known. Furthermore, effective disease-modifying therapies for any of these neurodegenerative disorders associated with ATXN1 mutations, including SCA1, FTD, and AD, are extremely limited or non-existent. Recently, we have identified profound alterations in oligodendrocyte progenitor cells (OPCs) and oligodendrocytes (OLs) at early stages of SCA1 mice, which emerge around the onset of behavioral impairments and much earlier than PC degeneration. In this proposal, we plan to determine the precise impact of oligodendroglial deficits on neurodegenerative diseases, and to elucidate the mechanisms through which mutant and wild-type ataxin-1 regulate oligodendroglial differentiation and function. Aim 1 will employ conditional mouse genetic approaches to determine the degree to which oligodendroglial dysfunction contributes to different disease-related phenotypes using SCA1 as a model. Aim 2 will determine the cellular and molecular mechanisms through which ataxin-1 regulates oligodendroglial differentiation and function in the nervous system using in vivo and in vitro approaches. Aim 3 will expand the scope of the proposed study to human tissues and cells to examine oligodendroglial phenotypes. We anticipate that the research aims will provide fundamental insights into the role of oligodendroglia in neurodegenerative disease pathogenesis and progression, and uncover new mechanisms through which OPC differentiation into OLs is regulated. If successful, these studies will advance the importance of examining non-neuronal contributions to neurodegenerative diseases and reveal novel potential entry points for therapeutic intervention in disorders in which ATXN1 mutations are associated, including SCA1, FTD, and AD.


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: 2026 ( Subtotal = $682,034 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	000	5	1/7/2026	NON-COMPETING CONTINUATION	$613,830
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	001	5	2/23/2026	NON-COMPETING CONTINUATION	$68,204
														Subtotal = $682,034

Issue Date FY: 2025 ( Subtotal = $628,236 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	002	4	8/12/2025	NON-COMPETING CONTINUATION	$54,562
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	001	4	12/24/2024	NON-COMPETING CONTINUATION	$613,830
2025	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	000	3	10/17/2024	SUPPLEMENT FOR EXPANSION	-$40,156
														Subtotal = $628,236

Issue Date FY: 2024 ( Subtotal = $749,156 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	002	3	5/17/2024	NON-COMPETING CONTINUATION	$69,892
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	001	3	2/14/2024	SUPPLEMENT FOR EXPANSION	$45,221
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	003	3	5/24/2024	SUPPLEMENT FOR EXPANSION	$5,026
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	000	3	2/13/2024	NON-COMPETING CONTINUATION	$629,017
														Subtotal = $749,156

Issue Date FY: 2023 ( Subtotal = $759,139 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	001	2	1/12/2023	SUPPLEMENT FOR EXPANSION	$72,920
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	000	2	1/10/2023	NON-COMPETING CONTINUATION	$686,219
														Subtotal = $759,139

Issue Date FY: 2022 ( Subtotal = $711,344 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	000	1	2/17/2022	NEW	$686,219
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	002	1	8/26/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Aging Research	001	1	8/18/2022	SUPPLEMENT FOR EXPANSION	$25,125
														Subtotal = $711,344

Grand Total All Awards = $3,529,909

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigation of the role of ATXN1 in oligodendroglia and neurodegenerative diseases

Award Number: R01AG076154

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer