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Mitochondrial and Metabolic Dysfunction in Age-related Neurodegeneration

Award Number: P01AG014930
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2000
PERIOD OF PERFORMANCE END DATE: 03/31/2022

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Mitochondrial and Metabolic Dysfunction in Age-related Neurodegeneration - DESCRIPTION (provided by applicant): Age-related neurodegenerative diseases including Alzheimer's Disease (AD) are associated with mild impairment of oxidative metabolism, oxidative stress and accumulation of abnormal proteins. Diminished glucose metabolism and abnormal mitochondrial function are invariant features of AD. The changes occur early in the disease and can be plausibly linked to the pathology including the plaques, tangles and memory deficits. Our previous studies proved our underlying hypothesis that "mitochondrial dysfunction in age-related neurodegenerative diseases promotes the development of disease and impairs the ability of the brain to adapt". The current program project will test the underlying mechanism for those changes, and test multiple approaches for reversing the deficits. The underlying hypothesis for this proposal is that posttranslational modifications and transcription for key proteins of energy metabolism as well as plasticity genes are abnormal in AD and form effective therapeutic targets. Protein modifications that are sensitive to metabolic state including acetylation, methylation and succinylation may alter protein interactions in the mitochondria as well as the ability of proteins to modulate transcription. Activation of genes PGC-1alpha, NRF2/ARE that stimulate biogenesis and the relationship to selective sirtuins (NAD-dependent deacetylases) will be tested in mouse models of AD as well as cultured cells from humans and rodents. The cross talk of mitochondria with the nucleus and cytosol may promote fission, fusion, mitophagy or autophagy and alter transcription of TCA cycle genes. Changes in the expression of the proteins modulating the mitochondrial proteome composition may affect the energy metabolism and the contribution of mitochondria to oxidative stress. The plasticity genes and the modification of their transcription by acetylation and methylation directly link metabolism and transcription and plasticity. The reversible repression of plasticity associated gene expression and diminished learning and memory provide a mechanism for AD related changes and their reversal. Successful completion of the goals of these projects can be expected to provide new insights into neurodegenerative processes and contribute to novel approaches to ameliorating age-related 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: 2023 ( Subtotal = $0 )
2023	2020	THE WINIFRED MASTERSON BURKE MEDICAL RESEARCH INSTITUTE, INC	785 MAMARONECK AVE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	19	10/28/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $2,420,583 )
2020	2020	WINIFRED MASTERSON BURKE MEDICAL RESEARCH INSTITUTE, INC, THE	785 MAMARONECK AVE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	19	6/25/2020	NON-COMPETING CONTINUATION	$2,420,583
														Subtotal = $2,420,583

Issue Date FY: 2019 ( Subtotal = $2,420,583 )
2019	2019	WINIFRED MASTERSON BURKE MEDICAL RESEARCH INSTITUTE, INC, THE	785 MAMARONECK AVE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	001	18	9/24/2019	NON-COMPETING CONTINUATION	$0
2019	2019	WINIFRED MASTERSON BURKE MEDICAL RESEARCH INSTITUTE, INC, THE	785 MAMARONECK AVE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	18	5/7/2019	NON-COMPETING CONTINUATION	$2,420,583
														Subtotal = $2,420,583

Issue Date FY: 2018 ( Subtotal = $2,420,583 )
2018	2018	WINIFRED MASTERSON BURKE MEDICAL RESEARCH INSTITUTE, INC, THE	785 MAMARONECK AVE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	17	4/30/2018	NON-COMPETING CONTINUATION	$2,420,583
														Subtotal = $2,420,583

Issue Date FY: 2017 ( Subtotal = $2,420,583 )
2017	2017	WINIFRED MASTERSON BURKE MEDICAL RESEARCH INSTITUTE, INC, THE	785 MAMARONECK AVE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	001	16	6/22/2017	NON-COMPETING CONTINUATION	$242,060
2017	2017	WINIFRED MASTERSON BURKE MEDICAL RESEARCH INSTITUTE, INC, THE	785 MAMARONECK AVE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	16	4/17/2017	NON-COMPETING CONTINUATION	$2,178,523
														Subtotal = $2,420,583

Issue Date FY: 2016 ( Subtotal = $2,437,958 )
2016	2016	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	002	15	5/12/2016	COMPETING CONTINUATION	$0
2016	2016	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	001	15	5/10/2016	COMPETING CONTINUATION	$0
2016	2016	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	15	4/14/2016	COMPETING CONTINUATION	$2,437,958
														Subtotal = $2,437,958

Issue Date FY: 2014 ( Subtotal = $1,626,785 )
2014	2014	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	14	6/11/2014	NON-COMPETING CONTINUATION	$1,626,785
														Subtotal = $1,626,785

Issue Date FY: 2013 ( Subtotal = $1,537,309 )
2013	2013	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	13	5/14/2013	NON-COMPETING CONTINUATION	$1,537,309
														Subtotal = $1,537,309

Issue Date FY: 2012 ( Subtotal = $1,626,788 )
2012	2012	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	12	4/20/2012	NON-COMPETING CONTINUATION	$1,626,788
														Subtotal = $1,626,788

Issue Date FY: 2011 ( Subtotal = $1,626,781 )
2011	2011	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	11	6/21/2011	NON-COMPETING CONTINUATION	$1,626,781
														Subtotal = $1,626,781

Issue Date FY: 2010 ( Subtotal = $1,636,811 )
2010	2010	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	001	10	4/16/2010	COMPETING CONTINUATION	$1,636,811
2010	2009	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	9	4/15/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,636,811

Issue Date FY: 2009 ( Subtotal = $1,407,062 )
2009	2009	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Trans-NIH Recovery Act Research Support	001	9	6/23/2009	SUPPLEMENT FOR EXPANSION	$7,623
2009	2009	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	9	4/16/2009	NON-COMPETING CONTINUATION	$1,399,439
														Subtotal = $1,407,062

Issue Date FY: 2008 ( Subtotal = $1,360,888 )
2008	2008	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	8	4/2/2008	NON-COMPETING CONTINUATION	$1,360,888
														Subtotal = $1,360,888

Issue Date FY: 2007 ( Subtotal = $1,350,406 )
2007	2007	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	7	5/30/2007	NON-COMPETING CONTINUATION	$1,350,406
														Subtotal = $1,350,406

Issue Date FY: 2006 ( Subtotal = $1,395,983 )
2006	2006	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	6	6/29/2006	NON-COMPETING CONTINUATION	$1,395,983
														Subtotal = $1,395,983

Issue Date FY: 2005 ( Subtotal = $1,430,806 )
2005	2005	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	5	7/11/2005	COMPETING CONTINUATION	$1,430,806
														Subtotal = $1,430,806

Issue Date FY: 2003 ( Subtotal = $157,625 )
2003	2003	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	002	4	9/29/2003	SUPPLEMENT FOR EXPANSION	$57,751
2003	2003	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	001	4	9/15/2003	SUPPLEMENT FOR EXPANSION	$99,874
														Subtotal = $157,625

Issue Date FY: 2002 ( Subtotal = $1,159,399 )
2002	2002	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	4	5/13/2002	NON-COMPETING CONTINUATION	$1,159,399
														Subtotal = $1,159,399

Issue Date FY: 2001 ( Subtotal = $1,130,735 )
2001	2001	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	3	6/21/2001	NON-COMPETING CONTINUATION	$1,130,735
														Subtotal = $1,130,735

Issue Date FY: 2000 ( Subtotal = $1,126,239 )
2000	2000	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	2	7/28/2000	NON-COMPETING CONTINUATION	$1,126,239
														Subtotal = $1,126,239

Issue Date FY: 1999 ( Subtotal = $1,087,238 )
1999	1999	WINIFRED MASTERSON BURKE MEDICAL RESCH INSTITUTE, INC	785 MAMARONECK AVENUE	WHITE PLAINS	NY	10605	WESTCHESTER	USA	Aging Research	000	1	6/1/1999	NEW	$1,087,238
														Subtotal = $1,087,238

Grand Total All Awards = $31,781,145

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Mitochondrial and Metabolic Dysfunction in Age-related Neurodegeneration

Award Number: P01AG014930

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2000

PERIOD OF PERFORMANCE END DATE: 03/31/2022

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