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ATP13A2 and Susceptibility to Neurodegeneration

Award Number: R01ES031124
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/28/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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ATP13A2 and Susceptibility to Neurodegeneration - Project Summary/Abstract Age-related neurodegenerative diseases are an increasing health and economic threat for millions of people each year. Genetic susceptibility, environmental exposures, and age can all increase the risk of developing neurodegenerative conditions such as synucleinopathies and manganism. The ATPase ATP13A2 is associated with multiple age-related neurodegenerative conditions including Parkinson’s disease, the most common synucleinopathy, Neuronal Ceroid Lipofuscinosis, and manganism and may be an important protein linking key neurodegenerative disease risk factors. Identification of gene-environment interactions associated with neurodegeneration is an important step to early detection, prevention, and treatment. The objective of this proposal is to determine how ATP13A2 is involved in mitochondrial maintenance and how it interacts with environmental and genetic risk factors to cause neurodegeneration. It is hypothesized that loss of ATP13A2 function makes neurons more vulnerable to manganese and alpha-synuclein toxicity through mechanisms involved in mitochondrial maintenance including repair and clearance mechanisms. Further, this disruption may interact with aging and protein accumulation to produce enhanced neurodegeneration and behavioural dysfunction. Our recent data shows that loss of function of ATP13A2 in mice leads to an enhanced response to manganese and increased pathology in the brain. Guided by preliminary data this hypothesis will be tested by pursuing three specific aims: 1) Determine the impact of loss of ATP13A2 function on mitochondrial maintenance in vivo, 2) Assess the neurotoxic consequences of Mn exposure in the presence of ATP13A2 loss on mitochondrial function in brain and periphery, and 3) Identify the impact of loss of ATP13A2 function and increased alpha-synuclein burden on mitochondrial maintenance and bioenergetics in vivo. Results from these studies are expected to have a positive impact on our understanding of how gene-environment interactions can contribute to cellular dysfunction, neurodegeneration, and behavioral impairments.


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 = $329,485 )
2024	2024	NORTHEAST OHIO MEDICAL UNIVERSITY	4209 STATE ROUTE 44	ROOTSTOWN	OH	44272	PORTAGE	USA	Environmental Health	000	5	6/14/2024	NON-COMPETING CONTINUATION	$329,485
														Subtotal = $329,485

Issue Date FY: 2023 ( Subtotal = $329,485 )
2023	2023	NORTHEAST OHIO MEDICAL UNIVERSITY	4209 STATE ROUTE 44	ROOTSTOWN	OH	44272	PORTAGE	USA	Environmental Health	000	4	7/4/2023	NON-COMPETING CONTINUATION	$329,485
														Subtotal = $329,485

Issue Date FY: 2022 ( Subtotal = $330,822 )
2022	2022	NORTHEAST OHIO MEDICAL UNIVERSITY	4209 SR 44	ROOTSTOWN	OH	44272	PORTAGE	USA	Environmental Health	000	3	6/9/2022	NON-COMPETING CONTINUATION	$330,822
														Subtotal = $330,822

Issue Date FY: 2021 ( Subtotal = $334,767 )
2021	2021	NORTHEAST OHIO MEDICAL UNIVERSITY	4209 SR 44	ROOTSTOWN	OH	44272	PORTAGE	USA	Environmental Health	000	2	6/29/2021	NON-COMPETING CONTINUATION	$334,767
														Subtotal = $334,767

Issue Date FY: 2020 ( Subtotal = $334,767 )
2020	2020	NORTHEAST OHIO MEDICAL UNIVERSITY	4209 SR 44	ROOTSTOWN	OH	44272	PORTAGE	USA	Environmental Health	000	1	9/25/2020	NEW	$334,767
														Subtotal = $334,767

Grand Total All Awards = $1,659,326

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ATP13A2 and Susceptibility to Neurodegeneration

Award Number: R01ES031124

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/28/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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