Wednesday, January 15, 2025 1/15/2025

Role of microglial phagocytosis in prion diseases

Award Number: R01NS045585
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

Prion diseases or Transmissible Spongiform Encephalopathies are transmissible neurodegenerative diseases in humans and animals that have no treatment and are 100% lethal. The transformation of glia into reactive states is recognized as one of the major hallmarks of neurodegenerative diseases including prion, Alzheimer’s, and Parkinson’s diseases. Conflicting data exist on whether in prion diseases, reactive microglia are protective or deleterious. Microglia are regarded as the main cells in CNS responsible for phagocytosis, yet the role of microglia-driven phagocytosis in prion disease has never been systematically examined. The current project is designed to fill this knowledge gap. Our recent studies supported by a previous award revealed that microglia not only effectively phagocytose prions or PrPSc but also engulf viable neurons that do not display apoptotic markers. Our work suggests that PrPSc primes microglia for phagocytosis via activating phagocytic pathways that sense exposed galactose as an ‘eat-me’ signal. We hypothesize that the phenotype of microglia transforms with disease progression, changing from primarily protective at the early stages when microglia uptake PrPSc, to predominantly detrimental at the later stages when microglia also target viable neurons. Aim 1 will establish the timeline of PrPSc uptake and neuronal engulfment in prion-infected animals, and rigorously test whether reactive microglia associated with prion disease phagocytose viable neurons. Aim 2 will assess the role of the P2y12 receptor in microglial phagocytosis of neurons. This aim will use P2ry12 inhibitors approved by the FDA and a mouse model for the conditional knockout of P2ry12 in myeloid cells to test whether the depletion of P2ry12 slows down or reverses disease progression in prion-infected animals. Aim 3 will employ primary microglia isolated from prion-infected animals to test whether the engulfment of viable neurons is mediated by phagocytic pathways that sense exposed galactose. Furthermore, Aim 3 will examine the effect of a conditional knockout of CD11b, which constitutes the MAC-1 phagocytic receptor in myeloid cells, on disease progression in prion- infected animals. As a whole, this study will inform us as to whether phagocytic activity should be targeted as a potential therapeutic strategy for treating prion diseases. Among the goals of this application is a translational component that will test the effectiveness of FDA-approved inhibitors of P2y12 receptors applied after clinical onset.


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 = $617,991 )
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	2/13/2024	COMPETING CONTINUATION	$617,991
														Subtotal = $617,991

Issue Date FY: 2022 ( Subtotal = $508,003 )
2022	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	20	3/23/2022	NON-COMPETING CONTINUATION	$50,802
2022	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	20	1/28/2022	NON-COMPETING CONTINUATION	$457,201
														Subtotal = $508,003

Issue Date FY: 2021 ( Subtotal = $508,003 )
2021	2021	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	2/4/2021	NON-COMPETING CONTINUATION	$508,003
														Subtotal = $508,003

Issue Date FY: 2020 ( Subtotal = $508,003 )
2020	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	2/17/2020	NON-COMPETING CONTINUATION	$508,003
														Subtotal = $508,003

Issue Date FY: 2019 ( Subtotal = $894,251 )
2019	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	17	9/5/2019	NON-COMPETING CONTINUATION	$0
2019	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	17	7/22/2019	SUPPLEMENT FOR EXPANSION	$386,248
2019	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	2/13/2019	NON-COMPETING CONTINUATION	$508,003
														Subtotal = $894,251

Issue Date FY: 2018 ( Subtotal = $508,003 )
2018	2018	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	4/17/2018	COMPETING CONTINUATION	$508,003
2018	2016	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	7/31/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $508,003

Issue Date FY: 2016 ( Subtotal = $416,620 )
2016	2016	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	4/13/2016	EXTENSION WITH OR WITHOUT FUNDS	$416,620
														Subtotal = $416,620

Issue Date FY: 2015 ( Subtotal = $416,620 )
2015	2015	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	4/16/2015	NON-COMPETING CONTINUATION	$416,620
														Subtotal = $416,620

Issue Date FY: 2014 ( Subtotal = $412,453 )
2014	2014	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	4/22/2014	NON-COMPETING CONTINUATION	$412,453
														Subtotal = $412,453

Issue Date FY: 2013 ( Subtotal = $402,038 )
2013	2013	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	5/21/2013	NON-COMPETING CONTINUATION	$27,078
2013	2013	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	4/12/2013	NON-COMPETING CONTINUATION	$374,960
														Subtotal = $402,038

Issue Date FY: 2012 ( Subtotal = $441,709 )
2012	2012	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	6/13/2012	COMPETING CONTINUATION	$441,709
														Subtotal = $441,709

Issue Date FY: 2011 ( Subtotal = $294,000 )
2011	2011	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	5/30/2011	NON-COMPETING CONTINUATION	$294,000
														Subtotal = $294,000

Issue Date FY: 2010 ( Subtotal = $297,000 )
2010	2010	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	4/22/2010	NON-COMPETING CONTINUATION	$297,000
2010	2009	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	8	4/22/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$192,142
2010	2009	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	4/22/2010	NON-COMPETING CONTINUATION	-$192,142
														Subtotal = $297,000

Issue Date FY: 2009 ( Subtotal = $300,000 )
2009	2009	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	4/30/2009	NON-COMPETING CONTINUATION	$300,000
														Subtotal = $300,000

Issue Date FY: 2008 ( Subtotal = $300,000 )
2008	2008	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	5/13/2008	NON-COMPETING CONTINUATION	$300,000
														Subtotal = $300,000

Issue Date FY: 2007 ( Subtotal = $300,000 )
2007	2007	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/19/2007	COMPETING CONTINUATION	$300,000
														Subtotal = $300,000

Issue Date FY: 2006 ( Subtotal = $301,802 )
2006	2006	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	7/12/2006	NON-COMPETING CONTINUATION	$301,802
														Subtotal = $301,802

Issue Date FY: 2005 ( Subtotal = $309,066 )
2005	2005	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/19/2005	NON-COMPETING CONTINUATION	$309,066
														Subtotal = $309,066

Issue Date FY: 2004 ( Subtotal = $309,066 )
2004	2004	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/28/2004	NON-COMPETING CONTINUATION	$309,066
														Subtotal = $309,066

Issue Date FY: 2003 ( Subtotal = $309,066 )
2003	2003	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/30/2003	NEW	$309,066
														Subtotal = $309,066

Grand Total All Awards = $8,353,694

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of microglial phagocytosis in prion diseases

Award Number: R01NS045585

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer