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The role of cholesterol metabolic enzyme CYP46A1 and its metabolite 24S-hydroxycholesterol in ischemic stroke.

Award Number: R01NS128018
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY The overall objectives for this application are to determine the role of cholesterol metabolic enzyme CYP46A1 and its metabolite 24S-hydroxycholesterol (24S-HC) in ischemic stroke. Our central hypothesis is that activation of CYP46A1 results in increased production of 24S-HC, which contributes to ischemic brain injury through potentiation of NMDAR. To test our hypothesis, we will use a combination of in vitro and in vivo stroke models along with electrophysiology, calcium imaging and transgenic mice to pursue the following three specific aims: Aim 1. Determine the role of CYP46A1 in ischemic brain injury; Aim 2. Determine the role and molecular mechanism of 24S-HC in ischemic neuronal injury in vitro; Aim 3. Define the signaling cascade underlying the role of CYP46A1 in ischemic brain injury. Success of the proposed research will define the role of cholesterol metabolic enzyme CYP46A1 and its metabolite 24S-HC in ischemic brain injury.


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 = $344,350 )
2024	2024	THE MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/24/2024	NON-COMPETING CONTINUATION	$344,350
														Subtotal = $344,350

Issue Date FY: 2023 ( Subtotal = $355,000 )
2023	2023	MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/20/2023	NON-COMPETING CONTINUATION	$355,000
														Subtotal = $355,000

Issue Date FY: 2022 ( Subtotal = $355,000 )
2022	2022	MOREHOUSE SCHOOL OF MEDICINE, INC., THE	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/26/2022	NEW	$355,000
														Subtotal = $355,000

Grand Total All Awards = $1,054,350

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The role of cholesterol metabolic enzyme CYP46A1 and its metabolite 24S-hydroxycholesterol in ischemic stroke.

Award Number: R01NS128018

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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