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Mitochondrial DNA and Ape1 in Huntington's Disease

Award Number: SC1NS095380
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: 07/01/2015
PERIOD OF PERFORMANCE END DATE: 06/30/2021

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Mitochondrial DNA and Ape1 in Huntington's Disease - DESCRIPTION (provided by applicant): Substantial evidence suggests that oxidative stress and mitochondrial dysfunction may play a role in neurodegeneration associated with HD. However, the precise mechanism(s) by which mutant huntingtin (htt) causes mitochondrial dysfunction remain largely unknown. We recently demonstrated a regulatory role of Ape1, the major mammalian apurinic/apyrimidinic (AP) endonuclease that participates in the base excision repair (BER) pathway, on mitochondrial function. Thus, our main objective is to determine the mechanisms of Ape1-mediated mitochondrial dysfunction in the context of mutant htt. This proposal will test the hypothesis that mutant htt, in combination with age-related effects, mediates mitochondrial dysfunction and neurodegeneration by targeting Ape1, which in turn results in deficient repair of mtDNA. We propose to test our hypothesis using a combination of in vivo and in vitro models of HD and directly test our hypothesis by determining if: 1) age-related changes in Ape1 synaptic nerve terminals contribute to mtDNA damage, mitochondrial dysfunction and neurodegeneration in HD and 2) what mechanism(s) might trigger Ape1-associated mitochondrial dysfunction in the context of the htt mutation. This study is likely to provide insight into a possible regulatory mechanism of Ape1 in mutant htt-induced mt dysfunction and neurodegeneration.


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: 2022 ( Subtotal = -$519 )
2022	2018	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/14/2021	NON-COMPETING CONTINUATION	-$519
														Subtotal = -$519

Issue Date FY: 2021 ( Subtotal = -$6,505 )
2021	2019	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Restoration Program: Hurricanes Harvey, Maria, and Irma – non-construction	000	4	11/4/2020	SUPPLEMENT FOR EXPANSION	$0
2021	2019	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Restoration Program: Hurricanes Harvey, Maria, and Irma – non-construction	002	4	8/8/2021	SUPPLEMENT FOR EXPANSION	-$6,505
2021	2018	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	12/24/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = -$6,505

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	9/14/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $320,451 )
2019	2019	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Restoration Program: Hurricanes Harvey, Maria, and Irma – non-construction	001	4	4/12/2019	SUPPLEMENT FOR EXPANSION	$320,451
2019	2018	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/12/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $320,451

Issue Date FY: 2018 ( Subtotal = $325,791 )
2018	2018	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	7/25/2018	NON-COMPETING CONTINUATION	$325,791
														Subtotal = $325,791

Issue Date FY: 2017 ( Subtotal = $295,744 )
2017	2017	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/7/2017	NON-COMPETING CONTINUATION	$295,744
														Subtotal = $295,744

Issue Date FY: 2016 ( Subtotal = $339,541 )
2016	2016	UNIVERSITY OF PUERTO RICO - MEDICAL SCIENCE CAMPUS	POST OFFICE BOX 365067	SAN JUAN	PR			USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/12/2016	NON-COMPETING CONTINUATION	$339,541
														Subtotal = $339,541

Issue Date FY: 2015 ( Subtotal = $334,494 )
2015	2015	UNIVERSITY OF PUERTO RICO - MEDICAL SCIENCE CAMPUS	POST OFFICE BOX 365067	SAN JUAN	PR			USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/22/2015	NEW	$334,494
														Subtotal = $334,494

Grand Total All Awards = $1,608,997

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Mitochondrial DNA and Ape1 in Huntington's Disease

Award Number: SC1NS095380

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: 07/01/2015

PERIOD OF PERFORMANCE END DATE: 06/30/2021

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