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Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease

Award Number: R01AG064798
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2019
PERIOD OF PERFORMANCE END DATE: 06/02/2023

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Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease - The molecular and cellular mechanism involved in the etiology of Alzheimer’s disease (AD) is still not fully understood. The risk factors underlying the heterogeneity and multifactorial nature of AD may include genetic background, environment, life styles, and the status of key molecules, i.e. amyloid, tau, ApoE, TREM2, biometals (Ca2+, Mg2+, Cu2+, etc.) and others. The goal of this study is to explore the potential role of Mg2+ in neuronal cell protection under AD-like pathological conditions and the underlying molecular mechanisms. The rationale is that 1) Mg2+-deficiency is correlated to aging and AD pathology, and 2) elevated brain Mg2+ enhances learning and memory, reduces neuroinflammation, and protects cognitive functions and synaptic plasticity in AD animal models. Prior studies revealed that brain and serum Mg2+ levels are significantly lower in patients with AD than in age-matched normal subjects. Moreover, Mg2+ elevation enhanced learning and memory in aged rats, prevented synaptic loss and reversed cognitive deficits in APP/PS1 AD mice and streptozotocin-induced sporadic AD rat model, as well as reduced neuroinflammation in brain injury and APP/PS1 AD model. In light of these findings, dyshomeostasis of Mg2+ in the brain is believed to be involved in the progression of AD. In addition, Mg2+ itself is a nature antioxidant, an antagonist of Ca2+, and an essential cofactor for ATP, nucleic acids and over 600 enzyme systems. Thus collectively, the hypothesis is that Mg2+ protects neurons by serving as an antioxidant to reduce oxidative stress, inflammation, and synaptic loss. Aim 1 is to examine efficacy and mechanism of Mg2+ on reducing oxidative stress and neuroinflammation. Aim 2 is to examine efficacy and mechanism of Mg2+ on inhibiting Aβ-induced synaptic loss and dysfunction. First, the mechanisms of how Mg2+ enters the cells and reduces Aβ-induced oxidative stress and inflammation in vitro will be elucidated and followed by validation of its efficacy on oxidative stress & inflammation suppression in AD animal model. Next, the mechanisms of how Mg2+ protects neurons from Aβ-induced synaptic loss and dysfunction, as well as Aβ- induced tau hyperphosphorylation and mitochondrial fragmentation in vitro. Last, the efficacy of Mg2+ on synaptic plasticity and cognitive deficits amelioration in AD animal model will be validated.


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 = $704,354 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	002	5	6/30/2023	SUPPLEMENT FOR EXPANSION	-$6,400
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	000	5	5/22/2023	NON-COMPETING CONTINUATION	$704,354
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	001	5	5/23/2023	SUPPLEMENT FOR EXPANSION	$6,400
														Subtotal = $704,354

Issue Date FY: 2022 ( Subtotal = $779,705 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	000	4	5/17/2022	NON-COMPETING CONTINUATION	$702,916
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	001	4	5/18/2022	SUPPLEMENT FOR EXPANSION	$76,789
														Subtotal = $779,705

Issue Date FY: 2021 ( Subtotal = $757,456 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	001	3	6/29/2021	SUPPLEMENT FOR EXPANSION	$70,389
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	000	3	6/4/2021	NON-COMPETING CONTINUATION	$687,067
														Subtotal = $757,456

Issue Date FY: 2020 ( Subtotal = $679,229 )
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	001	2	6/4/2020	NON-COMPETING CONTINUATION	$679,229
2020	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	000	1	4/8/2020	NEW	$0
														Subtotal = $679,229

Issue Date FY: 2019 ( Subtotal = $681,595 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	000	1	9/13/2019	NEW	$681,595
														Subtotal = $681,595

Grand Total All Awards = $3,602,339

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Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease

Award Number: R01AG064798

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2019

PERIOD OF PERFORMANCE END DATE: 06/02/2023

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