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Biophysical determination of the underlying cause of α-Syn oligomer toxicity

Award Number: R35GM142869
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Biophysical determination of the underlying cause of α-Syn oligomer toxicity - ABSTRACT Parkinson disease (PD) is the second most common neurodegenerative disease that affects nearly 5 millions of people around the world. PD is associated with intracellular aggregation of α-synuclein (α-Syn), a small protein that is involved in the regulation of lipid metabolism and synaptic vesicle trafficking. A growing body of evidence suggests that alterations in lipid profile, which were observed in both brain and plasma, can be directly linked to the onset of α-Syn aggregation. We hypothesize that the toxicity of α-Syn aggregates is determined by their structure, which in turn is controlled by the lipid composition of neuronal membranes. Our group pioneered development of a label-free, non-invasive and non-destructive approach that can be used to determine the structural organization of individual α-Syn aggregates. We will use this innovative biophysical imaging approach to unravel protein secondary structure of α-Syn oligomers grown in the presence of different lipids. We will investigate toxicity of these oligomers on primary dopaminergic neurons from midbrain, striatal, and cortical areas of the mouse brains. This will reveal the relationship between the structure of α-Syn oligomers and their toxicity. The proposed work also aims to determine the extent to which α-Syn oligomers with different structures exert toxic effects to the specific subsets of neurons.


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: 2025 ( Subtotal = $283,213 )
2025	2025	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	5	7/14/2025	NON-COMPETING CONTINUATION	$283,213
														Subtotal = $283,213

Issue Date FY: 2024 ( Subtotal = $284,156 )
2024	2024	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	4	8/16/2024	NON-COMPETING CONTINUATION	$284,156
														Subtotal = $284,156

Issue Date FY: 2023 ( Subtotal = $485,053 )
2023	2023	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	3	8/17/2023	NON-COMPETING CONTINUATION	$285,053
2023	2023	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	2	7/12/2023	SUPPLEMENT FOR EXPANSION	$200,000
														Subtotal = $485,053

Issue Date FY: 2022 ( Subtotal = $285,908 )
2022	2022	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	2	7/26/2022	NON-COMPETING CONTINUATION	$285,908
														Subtotal = $285,908

Issue Date FY: 2021 ( Subtotal = $286,722 )
2021	2021	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	1	8/4/2021	NEW	$286,722
														Subtotal = $286,722

Grand Total All Awards = $1,625,052

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Biophysical determination of the underlying cause of α-Syn oligomer toxicity

Award Number: R35GM142869

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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