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Use of NMNAT chaperone activity against Alzheimer related proteinpathy.

Award Number: K01AG057815
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/01/2019
PERIOD OF PERFORMANCE END DATE: 02/29/2024

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Use of NMNAT chaperone activity against Alzheimer related proteinpathy. - PROJECT SUMMARY Alzheimer's disease is a progressive, irreversible neurological disorder that slowly destroys the ability to live independently by affecting memory and thinking skills. While few treatments currently help with some symptoms, no interventions have yet been demonstrated to delay the onset or slow the progression. Alzheimer's symptoms are caused by loss of neurons and synapses in the cerebral cortex and subcortical regions, zones where two neuropathological signs have been found: neurofibrillary tangles and Amyloid plaques. Neurofibrillary tangles and amyloid plaques are toxic protein aggregates mainly composed respectively by hyperphosphorylated Tau and amyloid fragment Aβ that cause cell death and neurodegeneration. One of the keys to reduce the neurodegeneration happening in Alzheimer's patients is to prevent or block the formation of these aggregates. NMNAT is an endogenous enzyme involved in cellular metabolism that is known for its neuroprotective functions, in particular in axon degeneration. Recently, it has been shown that NMNAT can protect cells from protein-aggregates-induced neurotoxic stress by acting as a chaperone. Chaperones are endogenous proteins responsible for the re-folding or degradation of misfolded proteins. The long term goal of this project is to investigate if NMNAT neuroprotective activity can be used in the treatment of Alzheimer's disease. The objective of this proposal is to determine if overexpression of NMNAT in two different animal models of Alzheimer's disease can delay or prevent the formation of neurofibrillary tangles and amyloid plaques. The central hypothesis of this study is that NMNAT chaperone activity is conserved throughout species and that it can be used in the proteinopathy aspect of Alzheimer's. Guided by promising data that showed NMNAT preventing the neurodegeneration caused by Tau in a drosophila model, our central hypothesis will be tested by pursuing two specific aims: (1) Determine if NMNAT has neuroprotective activity in Drosophila models of Alzheimer's Disease and (2) Determine if NMNAT has neuroprotective activity in a mouse model of Alzheimer's Disease. The rationale for the proposed research is that the results will make a lasting impact in the understanding of neuroprotective pathways that can lead to the treatment of Alzheimer's disease. The proposed research is therefore relevant to the mission of the NIA “to support and conduct genetic, biological, clinical, behavioral, social, and economic research related to the aging process, diseases and conditions associated with aging” and to the current priority of NIA to “Improve our understanding of Alzheimer's disease, other dementias of aging, and the aging brain”.


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: 2024 ( Subtotal = -$36,664 )
2024	2023	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Aging Research	000	5	7/8/2024	NON-COMPETING CONTINUATION	-$36,664
														Subtotal = -$36,664

Issue Date FY: 2023 ( Subtotal = $123,579 )
2023	2023	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Aging Research	000	5	11/15/2022	NON-COMPETING CONTINUATION	$123,579
														Subtotal = $123,579

Issue Date FY: 2022 ( Subtotal = $123,579 )
2022	2022	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Aging Research	000	4	11/30/2021	NON-COMPETING CONTINUATION	$123,579
														Subtotal = $123,579

Issue Date FY: 2021 ( Subtotal = $123,579 )
2021	2021	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Aging Research	000	3	12/16/2020	NON-COMPETING CONTINUATION	$123,579
														Subtotal = $123,579

Issue Date FY: 2020 ( Subtotal = $123,579 )
2020	2020	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Aging Research	000	2	11/22/2019	NON-COMPETING CONTINUATION	$123,579
														Subtotal = $123,579

Issue Date FY: 2019 ( Subtotal = $123,179 )
2019	2019	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Aging Research	000	1	1/16/2019	NEW	$123,179
														Subtotal = $123,179

Grand Total All Awards = $580,831

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Use of NMNAT chaperone activity against Alzheimer related proteinpathy.

Award Number: K01AG057815

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/01/2019

PERIOD OF PERFORMANCE END DATE: 02/29/2024

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