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Fluorescent IRE sensor for PD drug discovery

Award Number: R43AG058338
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2018
PERIOD OF PERFORMANCE END DATE: 10/31/2020

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Fluorescent IRE sensor for PD drug discovery - SUMMARY Parkinson's disease (PD) is a debilitating neurodegenerative disease that affects about 1-2% of the population over the age of 60. The pathological hallmark of PD is the presence of intracellular protein aggregates that cause the degeneration and then death of dopaminergic neurons in the substantia nigra. The presynaptic protein α-synuclein was found to be the main component of Lewy bodies and α-synuclein aggregation is believed to be the key event in PD pathogenesis. Past drug discovery efforts have been focused on preventing α-synuclein aggregation or increasing α-synuclein clearance. However, overexpression and knockdown studies in cell lines and animal models showed that altering intracellular α-synuclein protein levels can also regulate PD pathology. These results suggest that α-synuclein translation is a significant yet under explored target for PD drug discovery. A putative iron-responsive element (IRE) that exhibited high sequence and structural similarities with the ferritin IRE was found in the distal 5'-untranslated region of α-synuclein mRNA and studies suggest that this IRE plays a critical role in regulating α-synuclein translation. Thus far, there is no high-throughput drug discovery methods that can interrogate drug binding directly to RNA structures that control protein translation. This is needed to bypass artifact-prone protein reporters that are typically used to study translation inhibitors. Therefore, this phase I SBIR application aims to develop a fluorescence sensor that monitors drug binding to IREs and can enable high-throughput drug screens for compounds that specifically target α-synuclein's IRE and ultimately result in lead compounds that could eventually be developed into inhibitor of α-synuclein protein synthesis.


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: 2021 ( Subtotal = $0 )
2021	2018	LUCERNA INC.	760 PARKSIDE AVE STE 311	BROOKLYN	NY	11226	KINGS	USA	Aging Research	000	1	4/21/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	LUCERNA INC.	760 PARKSIDE AVE STE 311	BROOKLYN	NY	11226	KINGS	USA	Aging Research	000	1	7/27/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	LUCERNA INC.	760 PARKSIDE AVE STE 311	BROOKLYN	NY	11226	KINGS	USA	Aging Research	000	1	1/18/2019	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $221,896 )
2018	2018	LUCERNA INC.	760 PARKSIDE AVE STE 311	BROOKLYN	NY	11226	KINGS	USA	Aging Research	000	1	6/30/2018	NEW	$221,896
														Subtotal = $221,896

Grand Total All Awards = $221,896

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Fluorescent IRE sensor for PD drug discovery

Award Number: R43AG058338

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2018

PERIOD OF PERFORMANCE END DATE: 10/31/2020

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